Multifunctional AuPt Nanoparticles for Synergistic Photothermal and Radiation Therapy.

Background: Photothermal therapy (PTT) has gained considerable interest as an emerging modality for cancer treatment in recent years. Radiation therapy (RT) has been widely used in the clinic as a traditional treatment method. However, RT and PTT treatments are limited by side effects and penetration depth, respectively. In addition, hypoxia within the tumor can lead to increased resistance to treatment. Methods: We synthesized multiple sizes of AuPt by modulating the reaction conditions. The smallest size of AuPt was selected and modified with folic acid (FA) for PTT and RT synergy therapy. Various methods including transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FITR) are used to determine the structure and composition of AuPt-FA (AF). In addition, we researched the photothermal properties of AF with IR cameras and infrared lasers. Flow cytometry, colony formation assays, CCK8, and fluorescent staining for probing the treatment effect in vitro. Also, we explored the targeting of AF by TEM and In Vivo Imaging Systems (IVIS). In vivo experiments, we record changes in tumor volume and weight as well as staining of tumor sections (ROS, Ki67, and hematoxylin and eosin). Results: The AuPt with particle size of 16 nm endows it with remarkably high photothermal conversion efficiency (46.84%) and catalase activity compared to other sizes of AuPt (30 nm and 100 nm). AF alleviates hypoxia in the tumor microenvironment, leading to the production of more reactive oxygen species (ROS) during the treatment. In addition, the therapeutic effect was significantly enhanced by combining RT and PTT, with an apoptosis rate of 81.1% in vitro and an in vivo tumor volume reduction rate of 94.0% in vivo. Conclusion: These results demonstrate that AF potentiates the synergistic effect of PTT and RT and has the potential for clinical translation.

Janus particle-engineered structural lipiodol droplets for arterial embolization.

Embolization (utilizing embolic materials to block blood vessels) has been considered one of the most promising strategies for clinical disease treatments. However, the existing embolic materials have poor embolization effectiveness, posing a great challenge to highly efficient embolization. In this study, we construct Janus particle-engineered structural lipiodol droplets by programming the self-assembly of Janus particles at the lipiodol-water interface. As a result, we achieve highly efficient renal embolization in rabbits. The obtained structural lipiodol droplets exhibit excellent mechanical stability and viscoelasticity, enabling them to closely pack together to efficiently embolize the feeding artery. They also feature good viscoelastic deformation capacities and can travel distally to embolize finer vasculatures down to 40 µm. After 14 days post-embolization, the Janus particle-engineered structural lipiodol droplets achieve efficient embolization without evidence of recanalization or non-target embolization, exhibiting embolization effectiveness superior to the clinical lipiodol-based emulsion. Our strategy provides an alternative approach to large-scale fabricate embolic materials for highly efficient embolization and exhibits good potential for clinical applications.

Multifunctional nanoparticles precisely reprogram the tumor microenvironment and potentiate antitumor immunotherapy after near-infrared-II light-mediated photothermal therapy.

Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy. However, mild PTT alone usually fails to activate the immune response and prevent tumor metastasis. Herein, a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an effective PTT effect in the second near-infrared (NIR-II) window, is developed. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response. Copper ions are released in the acidic TME to promote the M1 polarization of tumor-associated macrophages. The model antigen OVA not only acts as a scaffold for nanoparticle growth but also promotes the maturation of dendritic cells, which primes naive T cells to stimulate adaptive immunity. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, which suppresses tumor growth and metastasis in a mouse melanoma model. The proposed therapeutic platform, CuS@OVA nanoparticles, may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies. STATEMENT OF SIGNIFICANCE: Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy, but usually fails to activate the immune response and prevent tumor metastasis. Herein, we develop a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an excellent PTT effect in the second near-infrared (NIR-II) window. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response by promoting the M1 polarization of tumor-associated macrophages and the maturation of dendritic cells. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, suppressing tumor growth and metastasis. The platform may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies.

The bioengineered and multifunctional nanoparticles in pancreatic cancer therapy: Bioresponisive nanostructures, phototherapy and targeted drug delivery.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Multifunctional nanoparticles for the treatment and diagnosis of osteosarcoma.

Osteosarcoma (OS) is a common primary malignant bone tumor in adolescents. Currently, the commonly used treatment strategies for OS include surgery, chemotherapy and radiotherapy. However, these methods have some problems that cannot be ignored, such as postoperative sequelae and severe side effects. Therefore, in recent years, researchers have been looking for other means to improve the treatment or diagnosis effect of OS and increase the overall survival rate of patients. With the development of nanotechnology, nanoparticles (NPs) have presented excellent properties in improving the therapeutic efficacy of drugs for OS. Nanotechnology makes it possible for NPs to combine various functional molecules and drugs to achieve multiple therapeutic effects. This review presents the important properties of multifunctional NPs for the treatment and diagnosis of OS and focuses on the research progress of common NPs applied for drug or gene delivery, phototherapy and diagnosis of OS, such as carbon-based quantum dots, metal, chitosan and liposome NPs. Finally, the promising prospects and challenges of developing multifunctional NPs with enhanced efficacy are discussed, which lays the foundation and direction for improving the future therapeutic and diagnostic methods of OS.

Photothermal Propelling and Pyroelectric Potential-Promoted Cell Internalization of Janus Nanoparticles and Pyroelectrodynamic Tumor Therapy.

Cancer phototherapy experiences limitations in tissue diffusion and cell internalization of phototherapeutic agents and dose-dependent side effects. Herein, Janus pyroelectric nanoparticles (NPs) are designed to generate self-powered motion and built-in electric fields to overcome the delivery barriers. Polydopamine (PDA) layers are partially coated on tetragonal BaTiO3 (tBT) NPs to prepare Janus tBT@PDA, and Au NPs are deposited on the PDA caps to obtain Janus tBT@PDA-Au NPs. Near-infrared (NIR) illumination of tBT@PDA-Au builds in situ pyroelectric potentials on NPs, which selectively affect the membrane potential of tumor cells rather than normal cells to enhance tumor cell internalization and produce reactive oxygen species (ROS) for pyroelectric dynamic therapy (PEDT). The asymmetric photothermal effect of the Janus NPs creates thermophoretic force to propel NP motion, which enhances tumor diffusion and cellular uptake of NPs and boosts cytotoxicity and intracellular ROS levels. The inoculation of Au NPs increases the photothermal effect, exhibits larger motion velocities, produces higher pyroelectric potentials, and elevates cellular uptake rates, resulting in significant induction of tumor cell apoptosis, suppression of tumor growth, and extension of animal survival. Thus, the concise design of tBT@PDA-Au/NIR treatment has achieved thermophoretic motion-promoted tissue diffusion, built-in electric field-enhanced cell internalization, and photothermal/PEDT-synergized antitumor efficacy.

Multifunctional Nanoparticles Codelivering Doxorubicin and Amorphous Calcium Carbonate Preloaded with Indocyanine Green for Enhanced Chemo-Photothermal Cancer Therapy.

Background: Multifunctional stimuli-responsive nanoparticles with photothermal-chemotherapy provided a powerful tool for improving the accuracy and efficiency in the treatment of malignant tumors. Methods: Herein, photosensitizer indocyanine green (ICG)-loaded amorphous calcium-carbonate (ICG@) nanoparticle was prepared by a gas diffusion reaction. Doxorubicin (DOX) and ICG@ were simultaneously encapsulated into poly(lactic-co-glycolic acid)-ss-chondroitin sulfate A (PSC) nanoparticles by a film hydration method. The obtained PSC/ICG@+DOX hybrid nanoparticles were characterized and evaluated by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). The cellular uptake and cytotoxicity of PSC/ICG@+DOX nanoparticles were analyzed by confocal laser scanning microscopy (CLSM) and MTT assay in 4T1 cells. In vivo antitumor activity of the nanoparticles was evaluated in 4T1-bearing Balb/c mice. Results: PSC/ICG@+DOX nanoparticles were nearly spherical in shape by TEM observation, and the diameter was 407 nm determined by DLS. Owing to calcium carbonate and disulfide bond linked copolymer, PSC/ICG@+DOX nanoparticles exhibited pH and reduction-sensitive drug release. Further, PSC/ICG@+DOX nanoparticles showed an effective photothermal effect under near-infrared (NIR) laser irradiation, and improved cellular uptake and cytotoxicity in breast cancer 4T1 cells. Importantly, PSC/ICG@+DOX nanoparticles demonstrated the most effective suppression of tumor growth in orthotopic 4T1-bearing mice among the treatment groups. In contrast with single chemotherapy or photothermal therapy, chemo-photothermal treatment by PSC/ICG@+DOX nanoparticles synergistically inhibited the growth of 4T1 cells. Conclusion: This study demonstrated that PSC/ICG@+DOX nanoparticles with active targeting and stimuli-sensitivity would be a promising strategy to enhance chemo-photothermal cancer therapy.

Targeting Proinflammatory Molecules Using Multifunctional MnO Nanoparticles to Inhibit Breast Cancer Recurrence and Metastasis.

Photothermal therapy (PTT) is an effective treatment modality that is highly selective for tumor suppression and is a hopeful alternative to traditional cancer therapy. However, PTT-induced inflammatory responses may result in undesirable side effects including increased risks of tumor recurrence and metastasis. Here we developed multifunctional MnO nanoparticles as scavengers of proinflammatory molecules to alleviate the PTT-induced inflammatory response. The MnO nanoparticles improve the PTT therapy by (1) binding and scavenging proinflammatory molecules to inhibit the proinflammatory molecule-induced Toll-like receptors (TLR) activation and nuclear factor kappa B (NF-κB) signaling; (2) inhibiting activated macrophage-induced macrophage recruitment; and (3) inhibiting tumor cell migration and invasion. In vivo experimental results showed that further treatment with MnO nanoparticles after laser therapy not only inhibited the PTT-induced inflammatory response and primary tumor recurrence but also significantly reduced tumor metastasis due to the scavenging activity. These findings suggest that MnO nanoparticles hold the potential for mitigating the therapy-induced severe inflammatory response and inhibiting tumor recurrence and metastasis.

Ferrocene-based multifunctional nanoparticles for combined chemo/chemodynamic/photothermal therapy.

Ferrocene and its derivatives have great potential for biomedical applications, but few related studies have been reported. In this study, copper ions and ferrocene derivatives were used for the first time to construct the ferrocene-based nanoparticles (Cu-Fc) with a hydrated particle size of approximately 220 nm. Their good photothermal conversion properties were verified in vitro and in vivo for the first time, indicating that they could be used as a novel photothermal agent for tumor treatment. In addition, the nanoparticles exhibited efficient Fenton effect under weakly acidic conditions, indicating that they can generate hydroxyl radicals (OH) to kill tumors in the weakly acidic environment of the tumor-specific microenvironment. More importantly, the nanoparticles can deplete glutathione (GSH), thus further enhancing Fenton effect-mediated chemodynamic therapy (CDT). Multifunctional ferrocene-based nanoparticles (DOX@Cu-Fc) were obtained after loading the chemotherapeutic drug doxorubicin hydrochloride (DOX). The results of in vitro and in vivo experiments showed that DOX@Cu-Fc could enhance tumor treatment by the combination of chemo/CDT/photothermal therapy (PTT).

Multifunctional nanoparticles of sinomenine hydrochloride for treat-to-target therapy of rheumatoid arthritis via modulation of proinflammatory cytokines.

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant of Sinomenium acutum (Thunb.) Rehd.et Wils. Currently, sinomenine hydrochloride (SIN) preparations, classified as a natural disease-modifying anti-rheumatic drug (nDMARD), have been used for therapy of rheumatoid arthritis (RA); however, the efficacy of SIN was seriously limited by its short half-life, low bioavailability, and dose-dependent adverse reactions. In this study, a biomimetic nanocomplex based on Prussian blue nanoparticles (PB NPs) was developed for overcoming clinical limitations of SIN and accordingly improving its efficacy. In vitro studies showed that the nanocomplexes significantly inhibited abnormal proliferation of fibroblast-like synoviocytes (FLSs) by scavenging reactive oxygen species (ROS) and inhibiting secretion of proinflammatory cytokines. In vivo imaging demonstrated that the improved immune-escape properties of the nanocomplexes resulted in markedly increased half-life of circulation and levels of accumulated drugs at arthritic sites of adjuvant-induced arthritis (AIA) rats. Notably, the nanocomplexes significantly suppressed joint inflammation and protected against bone destruction of AIA rats by inhibiting inflammatory cytokine secretion of the synovial macrophages and FLSs. These results indicate that the nanocomplexes provide an excellent carrier for controlled release and targeted accumulation of SIN within the arthritic sites, which consequently achieve disease-remitting effects of SIN on RA.

Novel multifunctional NIR-II aggregation-induced emission nanoparticles-assisted intraoperative identification and elimination of residual tumor.

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1-π-A-D2-R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.

Metal-organic framework-mediated multifunctional nanoparticles for combined chemo-photothermal therapy and enhanced immunotherapy against colorectal cancer.

Because of molecular heterogeneity in tumors, clinical outcomes of tumor treatment are not very satisfactory, and novel strategies are therefore needed to address this challenge. Combination therapy could efficiently enhance tumor treatment by stimulating multiple pathways, reducing the systemic toxicity of monotherapy, and regulating the tumor immune microenvironments. Herein, metal-organic framework MIL-100 (Fe) nanoparticles (NPs) were synthesized by a microwave-assisted method, and oxaliplatin (OXA) and indocyanine green (ICG) were then loaded into hyaluronic acid (HA)-modified MIL-100 NPs to obtain multifunctional nanoparticles (OIMH NPs). The OIMH NPs exhibited sensitive photoacoustic imaging (PAI) for imaging-guided therapy and showed a good synergistic effect by combining chemotherapy with photothermal therapy (PTT) to kill tumor cells. Immunogenic cell death (ICD) and activation of T cells induced by the chemo-photothermal therapy could sensitize for immune checkpoint blockade (aPD-L1) response, thus eliciting systemic antitumor immunity. Finally, tumor inhibition was observed, which could be attributed to the combination of chemotherapy, PTT, and aPD-L1. On the basis of the study findings, an innovative imaging-mediated combined therapeutic strategy involving multifunctional NPs was proposed, which might potentially offer a new clinical treatment for colorectal cancer. STATEMENT OF SIGNIFICANCE: The metal-organic framework-mediated chemo-photothermal therapy guided by photoacoustic imaging (PAI) is an accurate and effective approach for tumor inhibition, which can synergistically achieve immunogenic cell death and lead to an increasing infiltration of immune cells in the tumor microenvironment, thereby enhancing the sensitivity for immune checkpoint blockade (aPD-L1) therapy. This type of therapy can not only reduce the systemic toxicity caused by traditional treatment methods, but it can also solve the issue of low response of immune checkpoint blockade in colorectal cancer (CRC). Our study provides experimental evidence for using the combination of immunotherapy and chemo-photothermal therapy against CRC.

Mesoporous polydopamine-based multifunctional nanoparticles for enhanced cancer phototherapy.

Cancer phototherapy has attracted increasing attention for its effectiveness, relatively low side effect, and noninvasiveness. The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has been shown to exhibit promising prospects in cancer treatment. However, the tumor hypoxia, high level of intracellular glutathione (GSH), and insufficient photosensitizer uptake significantly limit the PDT efficacy. In this work, we combine oxygen supply, GSH depletion, and tumor targeting in one nanoplatform, folate-decorated mesoporous polydopamine nanoparticles (FA-MPPD) co-loaded with new indocyanine green (IR-820) and perfluorooctane (PFO) (IR-820/PFO@FA-MPPD), to overcome the PDT resistance for enhanced cancer PDT/PTT. IR-820/PFO@FA-MPPD exhibit efficient singlet oxygen generation and photothermal effect under 808 nm laser irradiation, GSH-promoted IR-820 release, and efficient cellular uptake, resulting in high intracellular reactive oxygen species (ROS) level under 808 nm laser irradiation and strong photocytotoxicity in vitro. Following intratumoral injection, IR-820/PFO@FA-MPPD can relieve tumor hypoxia sustainably by PFO-mediated oxygen transport and deplete intracellular GSH by the Michael addition reaction, which boost the PDT effect and lead to the most potent antitumor effect upon 808 nm laser irradiation. The multifunctional IR-820/PFO@FA-MPPD developed in this work offer a relatively simple and effective strategy to potentiate PDT for efficient cancer phototherapy.

Hyaluronic acid targeted and pH-responsive multifunctional nanoparticles for chemo-photothermal synergistic therapy of atherosclerosis.

Atherosclerosis is a global disease with an extremely high morbidity and fatality rate, so it is necessary to develop effective treatments to reduce its impact. In this work, we successfully prepared a multifunctional drug-loaded nano-delivery system with pH-responsive, CD44-targeted, and chemical-photothermal synergistic treatment. Dendritic mesoporous silica nanoparticles capped with copper sulfide (CuS) were synthesized via an oil-water biphase stratification reaction system; these served as the carrier material and encapsulated the anticoagulant drug heparin (Hep). The pH-sensitive Schiff base bond was used as a gatekeeper and targeting agent to modify hyaluronic acid (HA) on the surface of the nanocarrier. HA coating endowed the nanocomposite with the ability to respond to pH and target CD44-positive inflammatory macrophages. Based on this multifunctional nanocomposite, we achieved precise drug delivery, controlled drug release, and chemical-photothermal synergistic treatment of atherosclerosis. The in vitro drug release results showed that the nanocarriers exhibited excellent drug-controlled release properties, and could release drugs in the weakly acidic microenvironment of atherosclerotic inflammation. Cytotoxicity and cell uptake experiments indicated that nanocarriers had low cytotoxicity against RAW 264.7 cells. Modification of HA to nanocarriers can be effectively internalized by RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Combining CuS photothermal treatment with anti-atherosclerosis chemotherapy showed better effects than single treatment in vitro and in vivo. In summary, our research proved that H-CuS@DMSN-NC-HA has broad application prospects in anti-atherosclerosis.

Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer's Disease-like Pathogenesis by Inhibiting Aß Aggregation and Regulating Gut Microbiota.

Alzheimer's disease (AD) is a neurodegenerative disease associated with amyloid-ß (Aß) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Res-selenium-peptide nanocomposite to enable the application of Res for eliminating Aß aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and d-galactose(d-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 ± 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood-brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 ± 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with Aß and decreasing Aß aggregation, effectively inhibiting Aß deposition in the hippocampus; (2) decreasing Aß-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating Aß-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD.

Intelligent and spatiotemporal drug release based on multifunctional nanoparticle-integrated dissolving microneedle system for synergetic chemo-photothermal therapy to eradicate melanoma.

Cutaneous melanoma is one of the most common malignant skin cancer with high lethality. Chemotherapy and photothermal therapy are important and extensively studied treatment modalities for melanoma. However, these therapies still face some challenges, which severely restrict their further applications, such as unsatisfactory efficacy of monotherapy, nonspecific uptake and release during drug delivery, and unexpected adverse effects from system administration. Recently, the strategies of collaboration, functional modification, stimuli-responsive design, and topical administration all show great prospect for solving above problems. In this research, a multifunctional nanoparticle-integrated dissolving microneedle drug delivery system was constructed, in which the nanoparticles were prepared based on the framework with the incorporation of photothermal agent (CuS) into Zeolitic imidazolate framework-8 and functionalized by hyaluronic acid. This system can co-load multi-modal drugs, improve specific uptake and distribution of targeted tumor, deliver drug locally, and release drug intelligently and spatiotemporally, thereby promising a low-dose administration with high efficiency. The high inhibiting tumor performance and excellent systematic safety were verified both in vitro and in vivo. Together, this smart design overcame the drawbacks of monotherapy and conventional system administration. We believe the nanoparticle-integrated dissolving microneedles will be in prospect of clinical application for more superficial tumors with further delicate optimization. STATEMENT OF SIGNIFICANCE: Melanoma is one of the most common skin cancers with high lethality. Extensively studied chemotherapy and photothermal therapy still face some challenges, such as the limited therapeutic efficacy and the severe system adverse effects. In order to overcome these drawbacks, the multifunctional nanoparticle-integrated dissolving microneedles (DMNs) were designed. Especially, the nanoparticles could co-load multi-modal drugs, improve specific uptake, and release drug intelligently and spatiotemporally. The microneedles could increase the drug accumulation in tumor, thus achieving excellent therapeutic efficacy and reducing side effects. This system paved the way to a less invasive, more focused and efficient therapeutic strategy for melanoma therapy.

Imaging application and radiosensitivity enhancement of pectin decorated multifunctional magnetic nanoparticles in cancer therapy.

In this contribution, we report the fabrication of multifunctional nanoparticles with gold shell over an iron oxide nanoparticles (INPs) core. The fabricated system combines the magnetic property of INPs and the surface plasmon resonance of gold. The developed nanoparticles are coated with thiolated pectin (TPGINs), which provides stability to the nanoparticles dispersion and allows the loading of hydrophobic anticancer drugs. Curcumin (Cur) is used as the model drug and an encapsulation efficiency of approximately 80% in TPGINs is observed. Cytotoxicity study with HeLa cells shows that Cur-loaded TPGINs have better viability percent (~30%) than Cur alone (~40%) at a dose of 30 µg of TPGINs. Further, annexin V-PI assay demonstrated the enhanced anticancer activity of Cur-loaded TPGINs via induction of apoptosis. The use of TPGINs leads to a significant enhancement in generating reactive oxygen species (ROS) in HeLa cells through improved radiosensitization by gamma irradiation (0.5 Gy). TPGINs are further evaluated for imparting contrast in magnetic resonance imaging (MRI) with the r2 relaxivity in the range of 11.06-13.94 s-1 µg-1 mL when measured at 7 Tesla. These experimental results indicate the potential of TPGINs for drug delivery and MR imaging.

Precise engineering of acorn-like Janus nanoparticles for cancer theranostics.

The anisotropic Janus nanoparticles (JNPs) provide synergistic effects by concentrating multiple properties on a single carrier. Herein, we reported a novel and simple approach to fabricate acorn-like poly(acrylic acid)-mesoporous calcium phosphate/polydopamine (PAA-mCaP/PDA) JNPs, which were selectively functionalized with methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to obtain superior stability, while the other mCaP sides served as a storage space and passage for the anti-cancer drug of doxorubicin (DOX). The unique acorn-like PAA-mCaP/PDA-PEG JNPs were utilized as novel theranostic agents for photoacoustic (PA) imaging-guided synergistic cancer chemo-phototherapy. More importantly, this synthetic strategy can be applied to synthesize various mesoporous Janus nanocarriers, paving the way toward designed synthesis of acorn-like JNPs in nanomedicine, biosensing and catalysis. STATEMENT OF SIGNIFICANCE: The distinct acorn-like poly(acrylic acid)-mesoporous calcium phosphate/polydopamine Janus nanoparticles (PAA-mCaP/PDA JNPs) with a spherical-shaped PAA-mCaP core and PDA half-shell were fabricated for the first time. To achieve superior stability, the acorn-like PAA-mCaP/PDA JNPs were selectively functionalized with methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to obtain acorn-like PAA-mCaP/PDA-PEG JNPs. The resultant acorn-like PAA-mCaP/PDA-PEG JNPs own an excellent biocompatibility, high drug-loading contents, good photothermal conversion efficiency, photoacoustic (PA) imaging capacity and pH/NIR dual-responsive properties, enabling the acorn-like JNPs to be applied for PA imaging-guided synergistic cancer chemo-phototherapy. More importantly, the synthetic approach could be extended to prepare acorn-like mesoporous inorganic substances/PDA JNPs for specific applications.

A Smart Multifunctional Nanoparticle for Enhanced Near-Infrared Image-Guided Photothermal Therapy Against Gastric Cancer.

BACKGROUND: Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer. METHODS: Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model. RESULTS: The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo. CONCLUSION: Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer.

Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma.

The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma.