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1.
Pharmacol Res ; 176: 106080, 2022 02.
Article in English | MEDLINE | ID: mdl-35032663

ABSTRACT

Combination therapy system has become a promising strategy for achieving favorable antitumor efficacy. Herein, a novel oral drug delivery system with colon localization and tumor targeting functions was designed for orthotopic colon cancer chemotherapy and photothermal combinational therapy. The polydopamine coated nanodiamond (PND) was used as the photothermal carrier, through the coupling of sulfhydryl-polyethylene glycol-folate (SH-PEG-FA) on the surface of PND to achieve systematic colon tumor targeting, curcumin (CUR) was loaded as the model drug, and then coated with chitosan (CS) to achieve the long gastrointestinal tract retention and colon localization functions to obtain PND-PEG-FA/CUR@CS nanoparticles. It has high photothermal conversion efficiency and good photothermal stability and exhibited near-infrared (NIR) laser-responsive drug release behavior. Folate (FA) modification effectively promotes the intracellular uptake of nanoparticles by CT26 cells, and the combination of chemotherapy and photothermal therapy (CT/PTT) can enhance cytotoxicity. Compared with free CUR group, nanoparticles prolonged the gastrointestinal tract retention time, accumulated more in colon tumor tissues, and exhibited good photothermal effect in vivo. More importantly, the CT/PTT group exhibited satisfactory tumor growth inhibition effects with good biocompatibility in vivo. In summary, this oral drug delivery system is an efficient platform for chemotherapy and photothermal combinational therapy of orthotopic colon cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Colonic Neoplasms/therapy , Curcumin/administration & dosage , Folic Acid/administration & dosage , Indoles/administration & dosage , Nanodiamonds/administration & dosage , Polyethylene Glycols/administration & dosage , Polymers/administration & dosage , Administration, Oral , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Cell Line, Tumor , Cell Survival/drug effects , Colonic Neoplasms/metabolism , Combined Modality Therapy , Curcumin/chemistry , Curcumin/pharmacokinetics , Drug Liberation , Folic Acid/chemistry , Folic Acid/pharmacokinetics , Indoles/chemistry , Indoles/pharmacokinetics , Mice, Inbred BALB C , Nanodiamonds/chemistry , Photothermal Therapy , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Polymers/chemistry , Polymers/pharmacokinetics
2.
Pharm Dev Technol ; 26(9): 1010-1020, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34412566

ABSTRACT

This work focuses on the extrusion of a brittle, tacky, cationic copolymer i.e. Eudragit® E-100 to prepare filament and subsequent 3D printing of hollow capsular device using the extruded filament. An optimum amount of talc and triethyl citrate was used for the possible extrusion of the polymer. There was no thermal and chemical degradation of the polymer observed after extrusion confirmed by DSC and FTIR analysis. Microscopic analysis of the printed capsule showed the layer-by-layer manner of 3D printing. Capsule parts were printed according to the set dimensions (00 size) with minimal deviation. Printed capsule showed the soluble behaviour in gastric fluid pH 1.2 where within 15 min the encapsulated drug encounters with the dissolution medium and almost 70% drug was dissolved within 4 hr. In case of phosphate buffer pH 6.8, the printed capsule showed a longed swelling behaviour up to 12 hr and then gradually bursting of capsule occurred wherein more than 90% encapsulated drug was dissolved within 36 hr. Enteric coating of the printed capsule showed similar behaviour in alkaline medium that observed with non-enteric capsule. This indicates the potential application of this printed capsules for both gastric and intestinal specific delayed drug delivery by a single step enteric coating process.


Subject(s)
Acrylates/chemical synthesis , Acrylates/pharmacokinetics , Chemistry, Pharmaceutical/methods , Polymers/chemical synthesis , Polymers/pharmacokinetics , Printing, Three-Dimensional , Berberine/chemical synthesis , Berberine/pharmacokinetics , Capsules , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/pharmacokinetics , Drug Evaluation, Preclinical/methods , Drug Liberation , Tablets, Enteric-Coated
3.
AAPS PharmSciTech ; 22(5): 169, 2021 Jun 02.
Article in English | MEDLINE | ID: mdl-34080086

ABSTRACT

Lutein has been used as a dietary supplement for the treatment of eye diseases, especially age-related macular degeneration. For oral formulations, we investigated lutein stability in artificial set-ups mimicking different physiological conditions and found that lutein was degraded over time under acidic conditions. To enhance the stability of lutein upon oral intake, we developed enteric-coated lutein solid dispersions (SD) by applying a polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF), through a solvent-controlled precipitation method. The SD were characterized in crystallinity, morphology, and drug entrapment. In the dissolution profile of lutein SD, a F80 formulation showed resistance toward the acidic environment under simulated gastric conditions while exhibiting a bursting drug release under simulated intestinal conditions. Our results highlight the potential use of HPMCAS-LF as an effective matrix to enhance lutein bioavailability during oral delivery and to provide novel insights into the eye-care supplement industry, with direct benefits for the health of patients.


Subject(s)
Lutein/chemical synthesis , Lutein/pharmacokinetics , Methylcellulose/analogs & derivatives , Biological Availability , Chromatography, High Pressure Liquid/methods , Drug Liberation , Drug Stability , Humans , Methylcellulose/chemical synthesis , Methylcellulose/pharmacokinetics , Polymers/chemical synthesis , Polymers/pharmacokinetics , Solubility , Solvents , X-Ray Diffraction/methods
4.
Biomed Pharmacother ; 137: 111333, 2021 May.
Article in English | MEDLINE | ID: mdl-33571834

ABSTRACT

Immunotherapy that boosts the body's immune system to treat local and distant metastatic tumors has offered a new treatment option for cancer. However, cancer immunotherapy via systemic administration of immunotherapeutic agents often has two major issues of limited immune responses and potential immune-related adverse events in the clinic. Hydrogels, a class of three-dimensional network biomaterials with unique porous structures can achieve local delivery of drugs into tumors to trigger the antitumor immunity, resulting in amplified immunotherapy at lower dosages. In this review, we summarize the recent development of polymer-based hydrogels as drug release systems for local delivery of various immunotherapeutic agents for cancer immunotherapy. The constructions of polymer-based hydrogels and their local delivery of various drugs in tumors to achieve sole immunotherapy, and chemotherapy-, and phototherapy-combinational immunotherapy are introduced. Furthermore, a brief conclusion is given and existing challenges and further perspectives of polymer-based hydrogels for cancer immunotherapy are discussed.


Subject(s)
Drug Delivery Systems/methods , Hydrogels/pharmacokinetics , Hydrogels/therapeutic use , Immunotherapy/methods , Neoplasms/therapy , Polymers/pharmacokinetics , Polymers/therapeutic use , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Liberation , Humans , Hydrogels/chemistry , Neoplasms/immunology , Phototherapy/methods , Polymers/chemistry
5.
Food Chem ; 340: 127934, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-32890858

ABSTRACT

As the important compounds in black garlic, the physicochemical properties and bioactivities of melanoidin (MLD) were investigated in this study. The results showed that MLD possessed strong metal-ion chelating capacity and radical scavenging activities which were positively correlative with molecular weight (MW). During the simulated digestion in vitro, the ultraviolet absorption, browning degree and MW distribution of MLD remained the same as initial. It proved that the MLD from black garlic could be indigestible like the dietary fiber with little loss of volatile compounds and polysaccharides. Remarkably, the bioactivities of MLD were reduced significantly under the treatment of α-amylase or hydrochloric acid, while they were stable and retained over 60% after adding pepsin and pancreatin. This study provides fundamental evidences for further research and widely application of MLD and black garlic in the production of functional food or food additives.


Subject(s)
Antioxidants/chemistry , Garlic/chemistry , Polymers/chemistry , Polymers/pharmacology , Digestion , Hydrochloric Acid/chemistry , Iron Chelating Agents/chemistry , Molecular Weight , Polymers/pharmacokinetics , alpha-Amylases/chemistry
6.
Physiol Rep ; 8(18): e14572, 2020 09.
Article in English | MEDLINE | ID: mdl-32965782

ABSTRACT

Currently described hyperkalemia (HK) animal models are typically acute and cause significant distress and mortality to the animals, warranting new approaches for studying chronic HK in a more appropriate clinical setting. Using the spontaneously hypertensive rat (SHR) model as a more relevant disease template, as well as surgical (unilateral nephrectomy), dietary (3% potassium [K+ ] supplementation), and pharmacological (amiloride) interventions, we were able to stably induce HK on a chronic basis for up to 12 weeks to serum K+ elevations between 8 and 9 mmol/L, with minimal clinical stress to the animals. Short-term proof-of-concept and long-term chronic studies in hyperkalemic SHRs showed concomitant increases in serum aldosterone, consistent with the previously reported relationship between serum K+ and aldosterone. Treatment with the K+ binder patiromer demonstrated that the disease model was responsive to pharmacological intervention, with significant abrogation in serum K+ , as well as serum aldosterone to levels near baseline, and this was consistent in both short-term and long-term 12-week chronic studies. Our results demonstrate the feasibility of establishing a chronic HK disease state, and this novel HK animal model may be suitable for further evaluating the effects of long-term, K+ -lowering therapies on effects such as renal fibrosis and end-organ damage.


Subject(s)
Hyperkalemia/drug therapy , Hypertension/complications , Polymers/therapeutic use , Aldosterone/blood , Animals , Hyperkalemia/etiology , Male , Nephrectomy/adverse effects , Polymers/pharmacokinetics , Potassium/blood , Potassium/metabolism , Rats , Rats, Inbred SHR
7.
Carbohydr Polym ; 241: 116224, 2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32507183

ABSTRACT

Polypyrroles have shown great potential in photoacoustic imaging and photothermal therapy owing to its excellent photothermal conversion capabilities. However, the synthesis of polypyrrole-based nano-assemblies which have colloidal stability in biological buffers requires a number of steps, including the polymerization of pyrrole monomers, self-assembly of polypyrrole-based copolymers, and even an additional step to increase the biocompatibility of the nano-assemblies. Herein, a "polymerization/assembly" two-in-one synthesis is proposed for the first time to achieve the one-step synthesis of a new family of polypyrrole-based nano-assemblies, dextran-polypyrrole nano-assemblies (Dex-PPy NAs), under ambient conditions and in aqueous media. In addition, the approach employs tetravalent cerium ions as initiators which can initiate the polymerization of pyrrole monomers through the initiation of free radicals from dextran molecular chains. The resultant Dex-PPy NAs have a photothermal conversion efficiency reaching as high as 41 % and an excellent photostability. More importantly, the NAs with controllable nanoscale dimensions display no signs of cytotoxicity in both in vitro and in vivo studies owing to their biocompatible dextran "shell". An in vivo study further confirmed that the Dex-PPy NAs have excellent real-time photoacoustic imaging and photothermal therapy capabilities for malignant tumors. Therefore, this study represents an important step towards the scalable synthesis of polypyrrole-based nano-assemblies with photothermal/photoacoustic dual capabilities and enhanced biocompatibility.


Subject(s)
Biocompatible Materials/administration & dosage , Dextrans/administration & dosage , Nanostructures/administration & dosage , Neoplasms/diagnostic imaging , Neoplasms/therapy , Polymers/administration & dosage , Pyrroles/administration & dosage , Animals , Biocompatible Materials/pharmacokinetics , Cell Line, Tumor , Cell Survival/drug effects , Dextrans/pharmacokinetics , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Mice, Inbred BALB C , Photoacoustic Techniques , Phototherapy , Polymers/pharmacokinetics , Pyrroles/pharmacokinetics
8.
Nat Commun ; 11(1): 1724, 2020 04 07.
Article in English | MEDLINE | ID: mdl-32265490

ABSTRACT

Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have seldom been used as PTAs due to the unsatisfactory photothermal conversion efficiency resulting from the irregular packing of chromophores in the vesicle membranes. Here we report a nano-sized polymer vesicle from hyperbranched polyporphyrins with favorable photothermal stability and extraordinarily high photothermal efficiency (44.1%), showing great potential in imaging-guided PTT for tumors through in vitro and in vivo experiments. These excellent properties are attributed to the in situ supramolecular polymerization of porphyrin units inside the vesicle membrane into well-organized 1D monofilaments driven by π-π stacking. We believe the supramolecular polymerization-enhanced self-assembly process reported here will shed a new light on the design of supramolecular materials with new structures and functions.


Subject(s)
Cell Survival/drug effects , Hyperthermia, Induced/methods , Nanoparticles/chemistry , Phototherapy/methods , Polymers/chemistry , Porphyrins/chemistry , Animals , Circular Dichroism , Female , Humans , Hydrophobic and Hydrophilic Interactions , MCF-7 Cells , Membranes, Artificial , Mice , Mice, Nude , Microscopy, Electron, Scanning , Molecular Dynamics Simulation , NIH 3T3 Cells , Nanoparticles/therapeutic use , Nanoparticles/ultrastructure , Polymerization , Polymers/chemical synthesis , Polymers/pharmacokinetics , Polymers/therapeutic use , Porphyrins/chemical synthesis , Porphyrins/pharmacokinetics , Porphyrins/therapeutic use , Rats , Spectrometry, Fluorescence , Temperature , Transplantation, Heterologous
9.
Int J Nanomedicine ; 15: 1469-1480, 2020.
Article in English | MEDLINE | ID: mdl-32184599

ABSTRACT

PURPOSE: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC. METHODS: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS). RESULTS: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects. CONCLUSION: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Dendrimers/chemistry , Drug Delivery Systems/methods , Liver Neoplasms/drug therapy , Nanoparticles/administration & dosage , Sorafenib/administration & dosage , Animals , Antineoplastic Agents/administration & dosage , Carcinoma, Hepatocellular/pathology , Dendrimers/pharmacokinetics , Hep G2 Cells , Humans , Liver Neoplasms/pathology , Mice , Nanoparticles/chemistry , Polymers/chemistry , Polymers/pharmacokinetics , Vitamin E/chemistry , Xenograft Model Antitumor Assays
10.
J Control Release ; 311-312: 147-161, 2019 10.
Article in English | MEDLINE | ID: mdl-31476343

ABSTRACT

Versatile, multifunctional nanomaterials for theranostic approaches in cancer treatment are highly on demand in order to increase therapeutic outcomes. Here, we developed thermo-responsive nanogels equipped with the efficient near-infrared (NIR) transducing polymer polypyrrole (PPY) for combinational photothermal and chemotherapeutic therapy along with photoacoustic imaging ability. Long-term stability and water-dispersibility of PPY was achieved using semi-interpenetration method for in situ polymerization of PPY into hydrophilic thermo-responsive nanogels. The semi-interpenetrated nanogels of spherical shape and with hydrodynamic sizes of around 200 nm retained the temperature response behaviour and exhibit excellent photothermal transducing abilities in the NIR region. The PPY nanogels served as photoacoustic contrast agents, which allowed determination of biodistribution profiles ex vivo. In addition, we developed a new method for biodistribution determination based on the photothermal response of the nanogels with an accuracy down to 12.5 µg/mL. We examined the ability of the nanogels as photothermal agents and drug delivery systems in vitro and in vivo. We showed that they efficiently inhibit tumor growth with combinational effects of chemotherapeutics and photothermal treatment. Our work encourages further exploration of nanogels as functional stabilizing matrix for photothermal transducers and their application as drug delivery devices in combination with photothermal therapy and imaging.


Subject(s)
Antineoplastic Agents/administration & dosage , Contrast Media/administration & dosage , Drug Delivery Systems , Methotrexate/administration & dosage , Nanogels/administration & dosage , Polymers/administration & dosage , Pyrroles/administration & dosage , A549 Cells , Animals , Antineoplastic Agents/pharmacokinetics , Contrast Media/pharmacokinetics , Diagnostic Imaging , Female , Hot Temperature , Humans , Methotrexate/pharmacokinetics , Mice, Nude , Neoplasms/diagnostic imaging , Neoplasms/therapy , Photoacoustic Techniques , Phototherapy , Polymers/pharmacokinetics , Pyrroles/pharmacokinetics
11.
Nanoscale ; 11(45): 21759-21766, 2019 Nov 21.
Article in English | MEDLINE | ID: mdl-31482919

ABSTRACT

Constructing nanocarriers with high drug loading capacity is a challenge, which limits the effective delivery of drugs to solid tumors. Here, we reported a one-pot synthesis of hollow nanoparticles (NPs) encapsulated by doxorubicin (DOX) and modified with polydopamine (PDA) to form PDA@DOX NPs for breast cancer treatment. PDA@DOX NPs demonstrated exceptionally high capacity (53.16%) for loading DOX. In addition, when PDA@DOX NPs were administered systemically, they exhibited responsive aggregation in the tumor sites and demonstrated a good controlled release effect for DOX due to the weak acidic environment of the tumor sites and targeting near-infrared (NIR) light irradiation. The PDA outer layer absorbed the near-infrared (NIR) light and facilitated simultaneous generation of heat energy for destroying the tumor cells to release the drug upon NIR irradiation. Moreover, this NIR-activated combined/synergistic therapy exhibited remarkably complete tumor growth suppression in a breast cancer mouse model. Importantly, NPs exhibited a good ultrasound performance both in vitro and in vivo, which could monitor the treatment process. In conclusion, this NIR-activated PDA@DOX NP system is demonstrated as a good US-guided combination (chemotherapy + PTT) therapy platform with high loading capacity and controlled drug release characteristics, which is promising for the treatment of breast cancer.


Subject(s)
Doxorubicin , Hyperthermia, Induced , Indoles , Mammary Neoplasms, Experimental , Nanoparticles , Phototherapy , Polymers , Animals , Cell Line, Tumor , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Female , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/pharmacology , Mammary Neoplasms, Experimental/metabolism , Mammary Neoplasms, Experimental/pathology , Mammary Neoplasms, Experimental/therapy , Mice, Nude , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology
12.
ACS Appl Mater Interfaces ; 11(38): 34652-34662, 2019 Sep 25.
Article in English | MEDLINE | ID: mdl-31483604

ABSTRACT

Modern crises in implantable or indwelling blood-contacting medical devices are mainly due to the dual problems of infection and thrombogenicity. There is a paucity of biomaterials that can address both problems simultaneously through a singular platform. Taking cues from the body's own defense mechanism against infection and blood clotting (thrombosis) via the endogenous gasotransmitter nitric oxide (NO), both of these issues are addressed through the development of a layered S-nitroso-N-acetylpenicillamine (SNAP)-doped polymer with a blended selenium (Se)-polymer interface. The unique capability of the SNAP-Se-1 polymer composites to explicitly release NO from the SNAP reservoir as well as generate NO via the incorporated Se is reported for the first time. The NO release from the SNAP-doped polymer increased substantially in the presence of the Se interface. The Se interface was able to generate NO in the presence of S-nitrosoglutathione (GSNO) and glutathione (GSH), demonstrating the capability of generating NO from endogenous S-nitrosothiols (RSNO). Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) traced distribution of elemental Se nanoparticles on the interface and the surface properties were evaluated by surface wettability and roughness. The SNAP-Se-1 efficiently inhibited the growth of bacteria and reduced platelet adhesion while showing minimal cytotoxicity, thus potentially eliminating the risks of systemic antibiotic and blood coagulation therapy. The SNAP-Se-1 exhibited antibacterial activity of ∼2.39 and ∼2.25 log reductions in the growth of clinically challenging adhered Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. SNAP-Se-1 also significantly reduced platelet adhesion by 85.5% compared to corresponding controls. A WST-8-based cell viability test performed on NIH 3T3 mouse fibroblast cells provided supporting evidence for the potential biocompatibility of the material in vitro. These results highlight the prospective utility of SNAP-Se-1 as a blood-contacting infection-resistant biomaterial in vitro which can be further tuned by application specificity.


Subject(s)
Escherichia coli/growth & development , Polymers , S-Nitroso-N-Acetylpenicillamine , Selenium , Staphylococcus aureus/growth & development , Animals , Cell Line , Cell Survival/drug effects , Mice , NIH 3T3 Cells , Nanoparticles , Nitric Oxide/pharmacokinetics , Nitric Oxide/pharmacology , Platelet Adhesiveness/drug effects , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology , S-Nitroso-N-Acetylpenicillamine/chemistry , S-Nitroso-N-Acetylpenicillamine/pharmacokinetics , S-Nitroso-N-Acetylpenicillamine/pharmacology , Selenium/chemistry , Selenium/pharmacokinetics , Selenium/pharmacology , Swine
13.
Biomaterials ; 220: 119405, 2019 11.
Article in English | MEDLINE | ID: mdl-31408811

ABSTRACT

Multifunctional nanoplatforms with flexible architectures and tumor microenvironment response are highly anticipated within the field of thermoradiotherapy. Herein, the multifunctional nanoplatforms for thermoradiotherapy have been successfully constructed by the embedding of tungsten disulfide quantum dots (WS2 QDs) into mesoporous polydopamine nanosponges (MPDA NSs), followed by integration with manganese dioxide (MnO2). MPDA-WS2@MnO2, the resultant nanoplatforms, exhibit radiosensitization enhanced behavior and a capacity for responsive oxygen self-supplementation. The ingenious mesoporous structure of MPDA NSs serves as reservoir for the assembly of WS2 QDs to form MPDA-WS2 nanoparticles (NPs), in which WS2 QDs provide the radiation enhancement effect, whereas the MPDA NSs framework endows the MPDA-WS2@MnO2 with an excellent photothermal capability. Additionally, the integration of the MnO2 component works to decompose the tumor-overexpressed H2O2 and alleviate tumor hypoxia subsequently, which has been demonstrated to enhance radiotherapy performance considerably. Meanwhile, the prepared MPDA-WS2@MnO2 nanoplatforms have been evaluated as trimodality contrast agents for computed tomography (CT), multispectral optoacoustic tomography (MSOT), and tumor microenvironment-responsive T1-weighted magnetic resonance (MR) imaging that have the potential for real-time guidance and monitoring during cancer therapy. More importantly, when subjected to near infrared (NIR) laser irradiation and X-ray exposure, the tumor is found to be inhibited significantly through the process of combined thermoradiotherapy. The design concepts of embedding WS2 QDs into MPDA NSs and oxygen self-supplementing hold great potential for multimodal imaging-guided thermoradiotherapy of hypoxic cancer.


Subject(s)
Hyperthermia, Induced , Indoles/chemistry , Multimodal Imaging , Nanoparticles/chemistry , Neoplasms/therapy , Oxygen/pharmacology , Polymers/chemistry , Quantum Dots/chemistry , Tungsten/chemistry , Animals , Cell Death , Cell Line, Tumor , Cell Survival , Clone Cells , DNA Damage , Hemolysis , Indoles/blood , Indoles/pharmacokinetics , Magnetic Resonance Imaging , Mice , Nanoparticles/ultrastructure , Neoplasms/diagnosis , Phantoms, Imaging , Photoacoustic Techniques , Polymers/pharmacokinetics , Porosity , Temperature , Tissue Distribution , Tomography, X-Ray Computed , Treatment Outcome , Tumor Hypoxia , Tungsten/blood , Tungsten/pharmacokinetics
14.
Nanoscale ; 11(22): 11012-11024, 2019 Jun 06.
Article in English | MEDLINE | ID: mdl-31140527

ABSTRACT

The integration of chemotherapy and photothermal therapy into one nanoplatform has attracted much attention for synergistic tumor treatment, but the practical clinical applications were usually limited by their synergistic effects and low selectivity for disease sites. To overcome these limitations, a tumor-specific and pH/NIR dual-responsive multifunctional nanocarrier coated with mussel inspired polydopamine and further conjugated with targeting molecular hyaluronic acid (HA) was designed and fabricated for synergistic targeted chemo-photothermal therapy. The synthesized versatile nanoplatform displayed strong near-infrared absorption because of the successful formation of polydopamine coating. Furthermore, the nanosystem revealed high storage capacity for drugs and pH/NIR dual-responsive release performance, which could effectively enhance the chemo-photothermal therapy effect. With this smart design, in vitro experimental results confirmed that the drug loaded multifunctional nanoparticles could be efficiently taken up by cancer cells, and exhibited remarkable tumor cell killing efficiency and excellent photothermal properties. Meanwhile, significant tumor regression in the tumor-bearing mice model was also observed due to the combination of chemotherapy and photothermal therapy. Thus, this work indicated that the simple multifunctional nanoplatform can be applied as an efficient therapeutic agent for site-specific synergistic chemo-photothermal therapy.


Subject(s)
Doxorubicin , Hyaluronic Acid , Hyperthermia, Induced , Indoles , Nanoparticles , Neoplasms, Experimental/therapy , Photochemotherapy , Polymers , Silicon Dioxide , Animals , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Female , HeLa Cells , Humans , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacokinetics , Hyaluronic Acid/pharmacology , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/pharmacology , Mice , Mice, Nude , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology , Porosity , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacokinetics , Silicon Dioxide/pharmacology
15.
Acta Biomater ; 90: 337-349, 2019 05.
Article in English | MEDLINE | ID: mdl-30936037

ABSTRACT

A theranostic nanoplatform (DTX/PFH@PPy-FA) for multi-modal imaging-guided photothermal-chemotherapy has been constructed. Lipid-perfluorohexane (PFH) nanodroplet loaded with docetaxel (DTX) was coated with a polypyrrole (PPy) shell. Then the folic acid (FA) molecule with active tumor-targeting function was modified on the surface of PPy shell. Due to the good photothermal conversion performance, PPy shell can raise the temperature under the near infrared laser irradiation, which not only produces photothermal effect to kill tumor cells, but also promotes liquid-gas phase change of PFH, and produces ultrasound imaging effect. The results of photothermal experiment and imaging experiment confirmed that the obtained DTX/PFH@PPy-FA possessed good photothermal, photoacoustic imaging and ultrasound imaging effects in vitro and in vivo. The results of in vitro cell experiments showed that DTX/PFH@PPy-FA had a active targeting ability to tumor cells, and its photothermal-chemotherapy synergistically inhibited the proliferation of tumor cells. In vivo study on 4T1-bearing BALB/c mice indicated that the photothermal-chemotherapy of DTX/PFH@PPy-FA not only effectively inhibited the growth of 4T1 breast cancer, but also inhibited lung metastasis. This multifunctional nanoparticle is expected to become a new nanoplatform for the visualized photothermal-chemotherapy of cancer. STATEMENT OF SIGNIFICANCE: In this work, we presented a multi-modal imaging-guided photothermal-chemotherapy theranostic nanoplatform (DTX/PFH@PPy-FA) for visualized treatment of breast cancer. The docetaxel (DTX) loaded perfluorohexane (PFH) nanodroplets (DTX/PFH@SPC) were firstly prepared and then coated with polypyrrole shell (PPy). Then, PEGylated folic acid was covalently modified to obtain the folate-targeted multifunctional nanoparticle (DTX/PFH@PPy-FA). Due to the good photothermal conversion performance, PPy shell can raise the temperature under the near infrared laser irradiation, which not only produces photothermal effect to kill tumor cells, but also promotes liquid-gas phase change of PFH, and produces good ultrasound imaging effect. The PPy shell also imparts photoacoustic imaging characteristics to the nanoparticles. Experimental results show that our prepared DTX/PFH@PPy-FA possesses folic acid-mediated tumor targeting ability, ultrasound and photoacoustic imaging, and photothermal-chemotherapy synergistic effect. This multi-functional nanoparticle is expected to become a new platform for the visualized photothermal-chemotherapy of breast cancer.


Subject(s)
Coated Materials, Biocompatible , Docetaxel , Fluorocarbons , Hyperthermia, Induced , Infrared Rays , Mammary Neoplasms, Experimental , Nanoparticles , Phototherapy , Polymers , Pyrroles , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacokinetics , Coated Materials, Biocompatible/pharmacology , Docetaxel/chemistry , Docetaxel/pharmacokinetics , Docetaxel/pharmacology , Female , Fluorocarbons/chemistry , Fluorocarbons/pharmacokinetics , Fluorocarbons/pharmacology , HeLa Cells , Humans , Mammary Neoplasms, Experimental/metabolism , Mammary Neoplasms, Experimental/pathology , Mammary Neoplasms, Experimental/therapy , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology , Pyrroles/chemistry , Pyrroles/pharmacokinetics , Pyrroles/pharmacology
16.
Toxicol Sci ; 170(1): 123-132, 2019 07 01.
Article in English | MEDLINE | ID: mdl-30985900

ABSTRACT

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. Upconversion nanoparticle applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb, Er, Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin 9_29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, noncytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.


Subject(s)
Mammary Neoplasms, Experimental/diagnostic imaging , Nanoparticles/chemistry , Polymers/chemistry , Whole Body Imaging/methods , Animals , CHO Cells , Cell Line, Tumor , Cricetulus , Drug Evaluation, Preclinical , Erbium/chemistry , Escherichia coli/genetics , Fluorides/chemistry , Humans , Luminescent Measurements , Nanoparticles/metabolism , Nanoparticles/toxicity , Polymers/pharmacokinetics , Polymers/toxicity , Receptor, ErbB-2/genetics , Surface Properties , Thulium/chemistry , Tissue Distribution , Yttrium/chemistry
17.
ACS Appl Mater Interfaces ; 11(13): 12357-12366, 2019 Apr 03.
Article in English | MEDLINE | ID: mdl-30859807

ABSTRACT

Efficient intracellular delivery of exogenous macromolecules is a key operation in biological research and for clinical applications. Moreover, under particular in vitro or ex vivo conditions, harvesting the engineered cells that maintain good viability is also important. However, none of the methods currently available is truly satisfactory in all respects. Herein, a "two-in-one" platform based on a polydopamine/poly( N-isopropylacrylamide) (PDA/PNIPAAm) hybrid film is developed, showing high efficiency in both cargo delivery and cell harvest without compromising cell viability. Due to the strong photothermal effect of PDA in response to near-infrared irradiation, this film can deliver diverse molecules to a number of cell types (including three hard-to-transfect cells) with an efficiency of ∼99% via membrane-disruption mechanism. Moreover, due to the thermoresponsive properties of PNIPAAm, the cells are harvested from the film without compromising viability by simply decreasing the temperature. A proof-of-concept experiment demonstrates that, using this platform, "recalcitrant" endothelial cells can be transfected by the functional ZNF580 gene and the harvested transfected cells can be recultured with high retention of viability and improved migration. In general, this "two-in-one" platform provides a reliable, universally applicable approach for both intracellular delivery and cell harvest in a highly efficient and nondestructive way, with great potential for use in a wide range of biomedical applications.


Subject(s)
Acrylic Resins , Drug Delivery Systems , Human Umbilical Vein Endothelial Cells/metabolism , Hyperthermia, Induced , Indoles , Phototherapy , Polymers , Transfection , Acrylic Resins/chemistry , Acrylic Resins/pharmacokinetics , Acrylic Resins/pharmacology , HeLa Cells , Human Umbilical Vein Endothelial Cells/cytology , Humans , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/pharmacology , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology , Transcription Factors/biosynthesis , Transcription Factors/genetics
18.
Nat Commun ; 10(1): 1192, 2019 03 13.
Article in English | MEDLINE | ID: mdl-30867429

ABSTRACT

Development of photothermal materials which are able to harness sunlight and convert it to thermal energy seems attractive. Besides carbon-based nanomaterials, conjugated polymers are emerging promising photothermal materials but their facile syntheses remain challenging. In this work, by modification of a CBT-Cys click condensation reaction and rational design of the starting materials, we facilely synthesize conjugated polymers poly-2-phenyl-benzobisthiazole (PPBBT) and its dihexyl derivative with good photothermal properties. Under the irradiation of either sunlight-mimicking Xe light or near-infrared laser, we verify that PPBBT has comparable photothermal heating-up speed to that of star material single-wall carbon nanotube. Moreover, PPBBT is used to fabricate water-soluble NPPPBBT nanoparticles which maintain excellent photothermal properties in vitro and photothermal therapy effect on the tumours exposed to laser irradiation. We envision that our synthetic method provides a facile approach to fabricate conjugated polymers for more promising applications in biomedicine or photovoltaics in the near future.


Subject(s)
Hyperthermia, Induced/methods , Nanoparticles/radiation effects , Neoplasms/therapy , Theranostic Nanomedicine/methods , Ultraviolet Therapy/methods , Animals , Cell Line, Tumor/transplantation , Combined Modality Therapy/methods , Disease Models, Animal , Female , Humans , Hyperthermia, Induced/instrumentation , Lasers , Mice , Mice, Inbred BALB C , Microscopy, Electron, Transmission , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Polymers/administration & dosage , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/radiation effects , Tissue Distribution , Treatment Outcome , Ultraviolet Therapy/instrumentation
19.
Mater Sci Eng C Mater Biol Appl ; 96: 138-145, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30606519

ABSTRACT

The nanoplatform of synergistic chemo-photothermal therapy has superior advantages on antitumor. It is urgently needed to explore novel nanocarrier for improving photothermal performance in drug delivery process. Herein, we synthesized polydopamine doped mesoporous silica-coated reduced graphene oxide (rGO/MSN/PDA) by simply adding dopamine hydrochloride into the oil-water biphasic reaction system as a multifunctional drug carrier for anticancer treatment, which combines chemotherapy and photothermal therapy. The rGO/MSN/PDA showed nearly twice the photothermal conversion efficiency of mesoporous silica-coated graphene oxide (GO/MSN) due to the reduction of GO and doping with PDA. In addition, the rGO/MSN/PDA showed pH-response DOX release abilities, which means higher release of DOX in tumor cells. The cell experiments in vitro proved that rGO/MSN/PDA with better biocompatibility compare to GO/MSN might offer a promising tool for improving the therapeutic effects of hepatocellular carcinoma cells through synergistic chemo-photothermal therapy.


Subject(s)
Doxorubicin , Drug Carriers , Graphite , Hyperthermia, Induced , Indoles , Neoplasms/therapy , Phototherapy , Polymers , Silicon Dioxide , Cell Line, Tumor , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Graphite/chemistry , Graphite/pharmacokinetics , Graphite/pharmacology , Humans , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/pharmacology , Neoplasms/metabolism , Neoplasms/pathology , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacokinetics , Silicon Dioxide/pharmacology
20.
Acta Biomater ; 83: 414-424, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30366131

ABSTRACT

Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP-mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100 µg in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells.


Subject(s)
Apoptosis , Coated Materials, Biocompatible , Colorectal Neoplasms , Gold , Hyperthermia, Induced , Indoles , Metal Nanoparticles , Phototherapy , Polymers , Silver , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacokinetics , Coated Materials, Biocompatible/pharmacology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Gold/chemistry , Gold/pharmacokinetics , Gold/pharmacology , HCT116 Cells , Humans , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/pharmacology , Male , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Mice , Mice, Inbred BALB C , Mice, Nude , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/pharmacology , Silver/chemistry , Silver/pharmacokinetics , Silver/pharmacology , Xenograft Model Antitumor Assays
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