Platinum Nanoparticles: Green Synthesis and Biomedical Applications.

Platinum nanoparticles (PtNPs) have superior physicochemical properties and great potential in biomedical applications. Eco-friendly and economic approaches for the synthesis of PtNPs have been developed to overcome the shortcomings of the traditional physical and chemical methods. Various biogenic entities have been utilized in the green synthesis of PtNPs, including mainly plant extracts, algae, fungi bacteria, and their biomedical effects were assessed. Other biological derivatives have been used in the synthesis of PtNPs such as egg yolk, sheep milk, honey, and bovine serum albumin protein. The green approaches for the synthesis of PtNPs have reduced the reaction time, the energy required, and offered ambient conditions of fabrication. This review highlights the state-of-the-art methods used for green synthesis of PtNPs, synthesis parameters, and their reported biomedical applications.

Interplay of localized pyrene chromophores and π-conjugation in novel poly(2,7-pyrene) ladder polymers.

We present a detailed spectroscopic study, along with the synthesis, of conjugated, ladder-type 2,7-linked poly(pyrene)s. We observe a delocalization of the first singlet excited state along the polymer backbone, i.e., across the 2,7 linkage in the pyrene moiety, in contrast to earlier studies on conjugated 2,7-linked poly(pyrene)s without ladder structure. The electronic signature of the pyrene unit is, however, manifested in an increased lifetime and reduced oscillator strength as well as a modified vibronic progression in absorption of the singlet state compared to a ladder-type poly(para-phenylene) (MeLPPP). Furthermore, the reduced oscillator strength and increased lifetime slow down Förster-type energy transfer in films, where this transfer occurs to sites with increasing inter-chain coupling of H-type nature.

Very High Solid State Photoluminescence Quantum Yields of Poly(tetraphenylethylene) Derivatives.

Five different poly(arylene-diarylvinylene)s have been synthesized by reductive polyolefination starting from the corresponding bis(α,α-dichlorobenzyl)-substituted monomers and dicobaltoctacarbonyl as reducing agent. The resulting polymers all contain main chain tetraphenylethylene units. Thanks to the aggregation-induced emission effect, the corresponding polymer films show remarkably high photoluminescence quantum yields (PLQYs) of 32%-73%. The polymer with the highest PLQY is tested as solid state sensing material for the PL-quenching-based detection of nitroaromatic analytes (1,3,5-trinitrobenzene as prototypical analyte).

Conjugated Polymer Nanoparticle-Triplet Emitter Hybrids in Aqueous Dispersion: Fabrication and Fluorescence Quenching Behavior.

Conjugated polymer nanoparticles based on poly[9,9-bis(2-ethylhexyl)fluorene] and poly[N-(2,4,6-trimethylphenyl)-N,N-diphenylamine)-4,4'-diyl] are fabricated using anionic surfactant sodium dodecylsulphate in water by miniemulsion technique. Average diameters of polyfluorene and polytriarylamine nanoparticles range from 70 to 100 and 100 to 140 nm, respectively. The surface of the nanoparticles is decorated with triplet emitting dye, tris(2,2'-bipyridyl)ruthenium(II) chloride. Intriguing photophysics of aqueous dispersions of these hybrid nanoparticles is investigated. Nearly 50% quenching of fluorescence is observed in the case of dye-coated polyfluorene nanoparticles; excitation energy transfer is found to be the dominant quenching mechanism. On the other hand, nearly complete quenching of emission is noticed in polytriarylamine nanoparticle-dye hybrids. It is proposed that the excited state electron transfer from the electron-rich polytriarylamine donor polymer to Ru complex leads to the complete quenching of emission of polytriarylamine nanoparticles. The current study offers promising avenues for developing aqueous solution processed-electroluminescent devices involving a conjugated polymer nanoparticle host and Ru or Ir-based triplet emitting dye as the guest.

An innovative approach to detect circulating tumor cells.

In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis during cancer treatment. Even though continuous progress in research offers more and more tools to combat cancer, we still lack a proper arsenal of therapeutics. Especially in tumors with close to no targeting options, like triple-negative breast cancer, early detection is often the main difference between successful and failed therapy. When such tumors are detected too late, they may have already produced plenty of CTCs, likely causing metastasis, which is the primary reason for tumor-associated deaths. Detecting those CTCs early on could substantially impact therapy outcomes and the 5-year survival rate. In our study, we developed and evaluated a reliable and affordable CTC screening method based on flow cytometry and 5-aminolevulinic acid (5-ALA) staining. We successfully established a circulation model for 5-ALA and CTCs research and demonstrated that the method can detect an average of 11 ±â€¯3.3 CTCs out of 10,000 peripheral blood mononuclear cells, representing as low as approximately 0.1 % with a reasonable number of false positive events. Additionally, we present initial results on a theranostic approach using 5-ALA converted to protoporphyrin IX. The outcomes of this study might contribute significantly to the further development of CTC detection and the overall detection and treatment of cancer.

Evaluating the photodynamic efficacy of nebulized curcumin-loaded liposomes prepared by thin-film hydration and dual centrifugation: In vitro and in ovo studies.

Lung cancer, one of the most common causes of high mortality worldwide, still lacks appropriate and convenient treatment options. Photodynamic therapy (PDT) has shown promising results against cancer, especially in recent years. However, pulmonary drug delivery of the predominantly hydrophobic photosensitizers still represents a significant obstacle. Nebulizing DPPC/Cholesterol liposomes loaded with the photosensitizer curcumin via a vibrating mesh nebulizer might overcome current restrictions. In this study, the liposomes were prepared by conventional thin-film hydration and two other methods based on dual centrifugation. The liposomes' physicochemical properties were determined before and after nebulization, showing that liposomes do not undergo any changes. However, morphological characterization of the differently prepared liposomes revealed structural differences between the methods in terms of lamellarity. Internalization of curcumin in lung adenocarcinoma (A549) cells was visualized and quantified. The generation of reactive oxygen species because of the photoreaction was also proven. The photodynamic efficacy of the liposomal formulations was tested against A549 cells. They revealed different phototoxic responses at different radiant exposures. Furthermore, the photodynamic efficacy was investigated after nebulizing curcumin-loaded liposomes onto xenografted tumors on the CAM, followed by irradiation, and evaluated using positron emission tomography/computed tomography and histological analysis. A decrease in tumor metabolism could be observed. Based on the efficacy of curcumin-loaded liposomes in 2D and 3D models, liposomes, especially with prior film formation, can be considered a promising approach for PDT against lung cancer.

In vitro and in ovo photodynamic efficacy of nebulized curcumin-loaded tetraether lipid liposomes prepared by DC as stable drug delivery system.

Lung cancer is one of the most common causes of high mortality worldwide. Current treatment strategies, e.g., surgery, radiotherapy, chemotherapy, and immunotherapy, insufficiently affect the overall outcome. In this study, we used curcumin as a natural photosensitizer in photodynamic therapy and encapsulated it in liposomes consisting of stabilizing tetraether lipids aiming for a pulmonary drug delivery system against lung cancer. The liposomes with either hydrolyzed glycerol-dialkyl-glycerol tetraether (hGDGT) in different ratios or hydrolyzed glycerol-dialkyl-nonitol tetraether (hGDNT) were prepared by dual centrifugation (DC), an innovative method for liposome preparation. The liposomes' physicochemical characteristics before and after nebulization and other nebulization characteristics confirmed their suitability. Morphological characterization using atomic force and transmission electron microscopy showed proper vesicular structures indicative of liposomes. Qualitative and quantitative uptake of the curcumin-loaded liposomes in lung adenocarcinoma (A549) cells was visualized and proven. Phototoxic effects of the liposomes were detected on A549 cells, showing decreased cell viability. The generation of reactive oxygen species required for PDT and disruption of mitochondrial membrane potential were confirmed. Moreover, the chorioallantoic membrane (CAM) model was used to further evaluate biocompatibility and photodynamic efficacy in a 3D cell culture context. Photodynamic efficacy was assessed by PET/CT after nebulization of the liposomes onto the xenografted tumors on the CAM with subsequent irradiation. The physicochemical properties and the efficacy of tetraether lipid liposomes encapsulating curcumin, especially liposomes containing hGDNT, in 2D and 3D cell cultures seem promising for future PDT usage against lung cancer.

Visualization and Characterization of Liposomes by Atomic Force Microscopy.

Atomic force microscopy is a high-resolution and nonoptical technique used to visualize and characterize biological samples and surfaces. In pharmaceutical research and development (R&D) and quality control (QC), drug delivery systems, like liposomes with sizes in a nanometer range, are preferred samples to be studied through atomic force microscopy. The instrument can determine the sample's topography (e.g., height), morphology, and material properties (e.g., hardness, adhesiveness). Various measuring modes, e.g., intermittent contact (AC mode), can generate height (measured), lock-in amplitude, and lock-in phase data, revealing interesting details about the drug delivery system.In this study, empty and drug-loaded liposomes with various lipid compositions and sizes (50-800 nm) were visualized and characterized with state-of-the-art atomic force microscope (AFM). The main focus here was the preparation methods of the samples, instrumental settings, and pitfalls that can occur during the whole imaging process. Moreover, troubleshooting and postdata processing are essential for a high-quality outcome.

Photothermally Controlled Drug Release of Poly(d,l-lactide) Nanofibers Loaded with Indocyanine Green and Curcumin for Efficient Antimicrobial Photodynamic Therapy.

Chronic wound infections with antibiotic-resistant bacteria have become a significant problem for modern healthcare systems since they are often associated with high costs and require profound topical wound management. Successful wound healing is achieved by reducing the bacterial load of the wound and providing an environment that enhances cell growth. In this context, nanofibers show remarkable success because their structure offers a promising drug delivery platform that can mimic the native extracellular matrix and accelerate cell proliferation. In our study, single-needle electrospinning, a versatile and cost-efficient technique, was used to shape polymers into an applicable and homogeneous fleece capable of a photothermally triggered drug release. It was combined with antimicrobial photodynamic therapy, a promising procedure against resistant bacteria. Therefore, poly(d,l-lactide) nanofibers loaded with curcumin and indocyanine green (ICG) were produced for local antimicrobial treatment. The mesh had a homogeneous structure, and the nanofibers showed a smooth surface. Recordings with a thermal camera showed that near-infrared light irradiation of ICG increased the temperature (>44 °C) in the surrounding medium. Release studies confirmed more than 29% enhanced curcumin release triggered by elevated temperature. The antimicrobial activity was tested against the gram-positive strain Staphylococcus saprophyticus subsp. bovis and the gram-negative strain Escherichia coli DH5 alpha. The nanofibers loaded with both photosensitizers and irradiated with both wavelengths reduced the bacterial viability (~4.4 log10, 99.996%) significantly more than the nanofibers loaded with only one photosensitizer (<1.7 log10, 97.828%) or irradiated with only one wavelength (<2.0 log10, 98.952%). In addition, our formulation efficiently eradicated persistent adhered bacteria by >4.3 log10 (99.995%), which was also confirmed visually. Finally, the produced nanofibers showed good biocompatibility, proven by the cellular viability of mouse fibroblasts (L929). The data demonstrate that we have developed a new economic nanofiber formulation, which offers a triggered drug release, excellent antimicrobial properties, and good biocompatibility.

How to Xenograft Cancer Cells on the Chorioallantoic Membrane of a Fertilized Hen's Egg and Its Visualization by PET/CT and MRI.

The chorioallantoic membrane (CAM) of fertilized hen's eggs represents a unique and alternative model for cancer research. The CAM model provides an optimal platform for xenografting cancer cell lines and studying essential key factors. Tumor size and growth as well as angiogenesis can be investigated to evaluate the response of therapies and strategies against cancer. Preclinical imaging represented by magnetic resonance imaging and positron emission tomography/computed tomography can generate detailed anatomical and functional information and reveal excellent metabolic sensitivity. In the following, a guideline is introduced in order to find a simplified entrance to the CAM model in combination with modern preclinical imaging techniques. Finally, the presented procedures are additionally completed by histological studies in the form of hematoxylin and eosin as well as immunohistochemical staining.

Lipid-Coated Polymeric Nanoparticles for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinomas.

Next to alcohol and tobacco abuse, infection with human papillomaviruses (HPVs) is a major risk factor for developing head and neck squamous cell carcinomas (HNSCCs), leading to 350,000 casualties worldwide each year. Limited therapy options and drug resistance raise the urge for alternative methods such as photodynamic therapy (PDT), a minimally invasive procedure used to treat HNSCC and other cancers. We prepared lipid-coated polymeric nanoparticles encapsulating curcumin as the photosensitizer (CUR-LCNPs). The prepared CUR-LCNPs were in the nanometer range (153.37 ± 1.58 nm) and showed an encapsulation efficiency of 92.69 ± 0.03%. Proper lipid coating was visualized using atomic force microscopy (AFM). The CUR-LCNPs were tested in three HPVpos and three HPVneg HNSCC lines regarding their uptake capabilities and in vitro cell killing capacity, revealing a variable but highly significant tumor cell inhibiting effect in all tested HNSCC cell lines. No significant differences were detected between the HPVpos and HPVneg HNSCC groups (mean IC50: (9.34 ± 4.73 µmol/L vs. 6.88 ± 1.03 µmol/L), suggesting CUR-LCNPs/PDT to be a promising therapeutic option for HNSCC patients independent of their HPV status.

Photoactive Parietin-loaded nanocarriers as an efficient therapeutic platform against triple-negative breast cancer.

The application of photodynamic therapy has become more and more important in combating cancer. However, the high lipophilic nature of most photosensitizers limits their parenteral administration and leads to aggregation in the biological environment. To resolve this problem and deliver a photoactive form, the natural photosensitizer parietin (PTN) was encapsulated in poly(lactic-co-glycolic acid) nanoparticles (PTN NPs) by emulsification diffusion method. PTN NPs displayed a size of 193.70 nm and 157.31 nm, characterized by dynamic light scattering and atomic force microscopy, respectively. As the photoactivity of parietin is essential for therapy, the quantum yield of PTN NPs and the in vitro release were assessed. The antiproliferative activity, the intracellular generation of reactive oxygen species, mitochondrial potential depolarization, and lysosomal membrane permeabilization were evaluated in triple-negative breast cancer cells (MDA-MB-231 cells). At the same time, confocal laser scanning microscopy (CLSM) and flow cytometry were used to investigate the cellular uptake profile. In addition, the chorioallantoic membrane (CAM) was employed to evaluate the antiangiogenic effect microscopically. The spherical monomodal PTN NPs show a quantum yield of 0.4. The biological assessment on MDA-MB-231 cells revealed that free PTN and PTN NPs inhibited cell proliferation with IC50 of 0.95 µM and 1.9 µM at 6 J/cm2, respectively, and this can be attributed to the intracellular uptake profile as proved by flow cytometry. Eventually, the CAM study illustrated that PTN NPs could reduce the number of angiogenic blood vessels and disrupt the vitality of xenografted tumors. In conclusion, PTN NPs are a promising anticancer strategy in vitro and might be a tool for fighting cancer in vivo.

Modern Photodynamic Glioblastoma Therapy Using Curcumin- or Parietin-Loaded Lipid Nanoparticles in a CAM Model Study.

Natural photosensitizers, such as curcumin or parietin, play a vital role in photodynamic therapy (PDT), causing a light-mediated reaction that kills cancer cells. PDT is a promising treatment option for glioblastoma, especially when combined with nanoscale drug delivery systems. The curcumin- or parietin-loaded lipid nanoparticles were prepared via dual asymmetric centrifugation and subsequently characterized through physicochemical analyses including dynamic light scattering, laser Doppler velocimetry, and atomic force microscopy. The combination of PDT and lipid nanoparticles has been evaluated in vitro regarding uptake, safety, and efficacy. The extensive and well-vascularized chorioallantois membrane (CAM) of fertilized hen's eggs offers an optimal platform for three-dimensional cell culture, which has been used in this study to evaluate the photodynamic efficacy of lipid nanoparticles against glioblastoma cells. In contrast to other animal models, the CAM model lacks a mature immune system in an early stage, facilitating the growth of xenografts without rejection. Treatment of xenografted U87 glioblastoma cells on CAM was performed to assess the effects on tumor viability, growth, and angiogenesis. The xenografts and the surrounding blood vessels were targeted through topical application, and the effects of photodynamic therapy have been confirmed microscopically and via positron emission tomography and X-ray computed tomography. Finally, the excised xenografts embedded in the CAM were analyzed histologically by hematoxylin and eosin and KI67 staining.

Editorial on the "Special Issue in Honor of Dr. Michael Weber's 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications".

Thousands of years ago, phototherapy or heliotherapy was performed by ancient Egyptians, Greeks, and Romans [...].

SmartFilm Tablets for Improved Oral Delivery of Poorly Soluble Drugs.

(1) Background: Numerous oral drugs exhibit limited bioavailability due to their poor solubility and poor intestinal permeability. The smartFilm technology is an innovative approach that improves the drug aqueous solubility via incorporating the drug in an amorphous state into a cellulose-based matrix, i.e., paper. smartFilms can be transformed into a free-flowing physical form (i.e., paper granules) that can be compressed into tablets with optimum physico-chemical and pharmaceutical properties. The aim of this study was to investigate if smartFilm tablets are suitable for improved oral delivery of poorly water-soluble drugs. (2) Methods: Curcumin is a poorly soluble drug with low intestinal permeability and was used for the production of curcumin-loaded smartFilms. The curcumin-loaded smartFilms were transferred into smartFilm granules which were then compressed into curcumin-loaded smartFilm tablets. The tablets were characterized regarding their physico-chemical and pharmaceutical properties, and the intestinal permeability of curcumin was determined with the ex vivo porcine intestinal model. The ex vivo intestinal permeability of curcumin from the smartFilm tablets was compared to a physical mixture of curcumin and paper and to a classical and to an innovative commercial product, respectively. (3) Results: The produced curcumin-loaded smartFilm tablets fulfilled the European Pharmacopoeia requirements, incorporated curcumin in amorphous state within the cellulose matrix and exhibited an enhanced dissolution rate. The ex vivo intestinal permeation data were shown to correlate to the in vitro dissolution data. The ex vivo intestinal permeation of curcumin from the smartFilm tablets was about two-fold higher when compared to the physical mixture and the classical commercial product. No differences in the ex vivo bioavailability were found between the smartFilm tablets and the innovative commercial product. (4) Conclusions: smartFilm tablets are a cost-effective and industrially feasible formulation approach for the formulation of poorly water-soluble drugs, i.e., BCS class II and IV drugs.

Highly Stable Liposomes Based on Tetraether Lipids as a Promising and Versatile Drug Delivery System.

Conventional liposomes often lack stability, limiting their applicability and usage apart from intravenous routes. Nevertheless, their advantages in drug encapsulation and physicochemical properties might be helpful in oral and pulmonary drug delivery. This study investigated the feasibility and stability of liposomes containing tetraether lipids (TEL) from Thermoplasma acidophilum. Liposomes composed of different molar ratios of TEL:Phospholipon 100H (Ph) were produced and exposed to various temperature and pH conditions. The effects on size, polydispersity index, and zeta potential were examined by dynamic and electrophoretic light scattering. Autoclaving, which was considered an additional process step after fabrication, could minimize contamination and prolong shelf life, and the stability after autoclaving was tested. Moreover, 5(6)-carboxyfluorescein leakage was measured after incubation in the presence of fetal calf serum (FCS) and lung surfactant (Alveofact). The incorporation of TEL into the liposomes significantly impacted the stability against low pH, higher temperatures, and even sterilization by autoclaving. The stability of liposomes containing TEL was confirmed by atomic force microscopy as images revealed similar sizes and morphology before and after incubation with FCS. It could be concluded that increasing the molar ratio in the TEL:Ph liposome formulations improved the structural stability against high temperature, low pH, sterilization via autoclaving, and the presence of FCS and lung surfactant.

Thermoresponsive Liposomes for Photo-Triggered Release of Hypericin Cyclodextrin Inclusion Complex for Efficient Antimicrobial Photodynamic Therapy.

Antimicrobial strategies with high efficacy against bacterial infections are urgently needed. The development of effective therapies to control bacterial infections is still a challenge. Herein, near-infrared (NIR)-activated thermosensitive liposomes (TSL) were loaded with the NIR-dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) and the water-soluble hypericin (Hyp) ß-cyclodextrin inclusion complex (Hyp-ßCD). DiR and Hyp-ßCD loaded thermosensitive liposomes (DHßCD-TSL) are functionalized for photothermal triggered release and synergistic photodynamic therapy to eliminate the gram-positive Staphylococcus saprophyticus. The dually active liposomes allow the production of heat and singlet oxygen species with the help of DiR and Hyp, respectively. The elevated temperature, generated by the NIR irradiation, irreversibly damages the bacterial membrane, increases the permeation, and melts the liposomes via a phase-transition mechanism, which allows the release of the Hyp-ßCD complex. The photodynamic effect of Hyp-ßCD eradicates the bacterial cells owing to its toxic oxygen species production. DHßCD-TSL measured the size of 130 nm with an adequate encapsulation efficiency of 81.3% of Hyp-ßCD. They exhibited a phase transition temperature of 42.3 °C, while they remained stable at 37 °C, and 44% of Hyp-ßCD was released after NIR irradiation (T > 47 °C). The bacterial viability dropped significantly after the synergistic treatment (>4 log10), indicating that the NIR-activated TSL have immense therapeutic potential to enhance the antibacterial efficacy. The liposomes showed good biocompatibility, which was confirmed by the cellular viability of mouse fibroblasts (L929).

Parietin Cyclodextrin-Inclusion Complex as an Effective Formulation for Bacterial Photoinactivation.

Multidrug resistance in pathogenic bacteria has become a significant public health concern. As an alternative therapeutic option, antimicrobial photodynamic therapy (aPDT) can successfully eradicate antibiotic-resistant bacteria with a lower probability of developing resistance or systemic toxicity commonly associated with the standard antibiotic treatment. Parietin (PTN), also termed physcion, a natural anthraquinone, is a promising photosensitizer somewhat underrepresented in aPDT because of its poor water solubility and potential to aggregate in the biological environment. This study investigated whether the complexation of PTN with (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) could increase its solubility, enhance its photophysical properties, and improve its phototoxicity against bacteria. At first, the solubilization behavior and complexation constant of the PTN/HP-ß-CD inclusion complexes were evaluated by the phase solubility method. Then, the formation and physicochemical properties of PTN/HP-ß-CD complexes were analyzed and confirmed in various ways. At the same time, the photodynamic activity was assessed by the uric acid method. The blue light-mediated photodegradation of PTN in its free and complexed forms were compared. Complexation of PTN increased the aqueous solubility 28-fold and the photostability compared to free PTN. PTN/HP-ß-CD complexes reduce the bacterial viability of Staphylococcus saprophyticus and Escherichia coli by > 4.8 log and > 1.0 log after irradiation, respectively. Overall, the low solubility, aggregation potential, and photoinstability of PTN were overcome by its complexation in HP-ß-CD, potentially opening up new opportunities for treating infections caused by multidrug-resistant bacteria.

Thermosensitive Liposomes Encapsulating Nedaplatin and Picoplatin Demonstrate Enhanced Cytotoxicity against Breast Cancer Cells.

Thermosensitive liposomes (TSL) have been used for localized temperature-responsive release of chemotherapeutics into solid cancers, with a minimum of one invention currently in clinical trials (phase III). In this study, TSL was designed using a lipid blend comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (DSPE-PEG-2000) (molar ratio of 88:9:2.8:0.2). Either nedaplatin (ND) or p-sulfonatocalix[4]arene-nedaplatin was encapsulated in the aqueous inner layer of TSL to form (ND-TSL) or p-SC4-ND-TSL, respectively. The hydrophobic platinum-based drug picoplatin (P) was loaded into the external lipid bilayer of the TSL to develop P-TSL. The three nanosystems were studied in terms of size, PDI, surface charge, and on-shelf stability. Moreover, the entrapment efficiency (EE%) and release % at 37 and 40 °C were evaluated. In a 30 min in vitro release study, the maximum release of ND, p-SC4-ND, and picoplatin at 40 °C reached 74, 79, and 75%, respectively, compared to approximately 10% at 37 °C. This demonstrated temperature-triggered drug release from the TSL in all three developed systems. The designed TSL exhibited significant in vitro anticancer activity at 40 °C when tested on human mammary gland/breast adenocarcinoma cells (MDA-MB-231). The cytotoxicity of ND-TSL, p-SC4-ND-TSL, and P-TSL at 40 °C was approximately twice those observed at 37 °C. This study suggests that TSL is a promising nanoplatform for the temperature-triggered release of platinum-based drugs into cancer cells.

Co-delivery of carbonic anhydrase IX inhibitor and doxorubicin as a promising approach to address hypoxia-induced chemoresistance.

Hypoxia, an oxygen-deprived condition of the tumor, is one of the major reasons for resistance to chemotherapy. Carbonic anhydrases are generally involved in pH homeostasis in normal conditions, but in solid tumors having a strong relation with hypoxia, the carbonic anhydrase IX (CA-IX) enzyme is overexpressed and results in an extracellular acidic environment. For most weakly basic anticancer drugs, including doxorubicin (Dox), the ionization in an acidic environment limits their cellular uptake, and consequently, the tumor exposure to the drug at sub-therapeutic concentration comes out as chemoresistance. Herein, a combined drug delivery system of liposomes and mesoporous silica nanoparticles (MSNPs) was developed for the co-delivery of the CA-IX enzyme inhibitor and Dox in hypoxic condition. The unique structure of MSNPs with higher surface area was utilized for higher drug loading and sustained release of Dox. Additionally, the biocompatible nature of liposomal coating as a second loading site for the CA-IX enzyme inhibitor has provided gatekeeping effects at pore opening to avoid premature drug release. Lipid coated MSNPs as a co-delivery system for Dox and the CA-IX inhibitor have synergistic cytotoxic effects against MDA-MB 231 breast cancer cells in hypoxic conditions. These findings assure the potential of this drug delivery system to overcome hypoxia-related chemoresistance.