Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression.

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

Hydrogel design to overcome thermal resistance and ROS detoxification in photothermal and photodynamic therapy of cancer.

Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (-)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.

Mn2+ /Ir3+ -Doped and CaCO3 -Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image-Guided Synergistic Cancer Therapy.

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

Development of superior nanotheranostic agents with indocyanine green-conjugated poly(styrene-alt-maleic acid) nanoparticles for tumor imaging and phototherapy.

Developing safe, high-quality theranostic agents for cancer treatment is of great clinical value. In this work, for the first time, the clinical indocyanine green (ICG) is coupled with the biocompatible poly(styrene-alt-maleic anhydride) (PSMAn) to obtain the PSMAn-ICG polymer. The self-assembly of its hydrolyzed product in water results in ICG-conjugated poly(styrene-alt-maleic acid) nanoparticles (PSMA-ICG NPs). Intriguingly, the NPs have many advantages, including good solubility and stability in aqueous solutions, high photostability and decreased hemolytic damage to red blood cells, highlighting the importance of PSMA coupling. More interestingly, PSMA-ICG NPs significantly promote tumor targeting and enable long-term imaging of tumors. Furthermore, the administration of PSMA-ICG NPs in combination with near-infrared laser irradiation provides superior potency in the photothermal therapy of tumors. Furthermore, 9-amino-sialic acid (Sia)-coated PSMA-ICG NPs are fabricated, further enhancing tumor imaging and phototherapy. This is the first report of PSMA-NIR conjugates achieving tumor reduction in mice. Overall, this study provides novel phototheranostic agents with broad clinical transformation prospects.

Analgesic and potentiated photothermal therapy with ropivacaine-loaded hydrogels.

Rationale: Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. Methods: The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. Results: PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8+ T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+ T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8+ T cells infiltration into tumor and potentiates PTT efficacy. Conclusion: This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.

Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO2/ICG@ZIF-8, which was capable of self-sufficient O2 delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO2 and indocyanine green (ICG) form CaO2/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO2 reacts with water under acidic conditions to produce O2 so CaO2/ICG@ZIF-8 has an excellent O2 supply capacity, which is essential for PDT. Moreover, CaO2/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO2/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO2/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both in vitro and in vivo studies. Notably, the Zn and Ca generated by CaO2/ICG@ZIF-8 degradation are essential elements for the body, so CaO2/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.

Engineering goat milk-derived extracellular vesicles for multiple bioimaging-guided and photothermal-enhanced therapy of colon cancer.

Multimodal image-guided photothermal therapy (PTT) has great application potential in cancer treatment due to its advantages of low side effects and good efficacy. There is an urgent need for PTT nanocarriers with high loading efficiency and modified surfaces. Goat milk-derived extracellular vesicles (GMVs) an ideal PTT nanoplatforms due to their anti-inflammatory ability, tumor retention ability, high yield, and high biosafety. This study used GMVs to design a theranostic nanoprobe for positron emission tomography/computer tomography/near-infrared fluorescence (PET/CT/NIRF) imaging and image-guided PTT for colon cancer. The key genes, important biological processes, and important signaling pathways of indocyanine green (ICG)-mediated PTT and N3-GMV@ICG-mediated PTT were analyzed. The nanoprobe triggered anti-tumor immune and inflammation responses to enhance PTT. In addition, the nanoprobe could attenuate PTT-induced inflammation benefiting from the anti-inflammatory efficacy of GMVs. Therefore, our findings conceptually advanced the diagnosis and treatment of colon cancer. We believed that the nanoprobe had broad clinical transformation prospects, and GMVs might be ideal nanocarriers for constructing integrated diagnostic and PTT probes.

Hyperthermia-sensitive Liposomes Containing Brucea Javanica Oil for Synergistic Photothermal-/Chemo-Therapy in Breast Cancer Treatment.

INTRODUCTION: High mortality and limited therapeutic efficacy of clinical treatment make breast cancer a stubborn disease in women. The hypovascular issue is the main challenge needed to be overcome in breast cancer treatment. METHODS: For this purpose, hyperthermia-sensitive liposomes containing indocyanine green (ICG) and brucea javanica oil (BJO) (LP(BJO/ICG)) were constructed for near-infrared (NIR) laser-induced photothermal- /chemo-antitumor therapy. ICG, an FDA-approved photothermal agent, was employed in this study to perform photothermal therapy (PTT) effect as well as relieve hypovascular conditions in breast cancer tissue. RESULTS: BJO triggered release from the hyperthermia-sensitive LP (BJO/ICG) due to disassembly of liposomes under the PTT effect caused by ICG under NIR laser irradiation. It was found that mice in LP (BJO/ICG) group showed the slowest tumor growth under NIR laser irradiation, illustrating the strongest antitumor effect among all groups. CONCLUSION: This responsive-release drug delivery platform can be a promising candidate for the treatment of breast cancer.

Hollow Nanooxidase Enhanced Phototherapy Against Solid Tumors.

Although phototherapy has attracted extensive attention in antitumor field in recent years, its therapeutic effect is usually unsatisfactory because of the complexity and variability of the tumor microenvironment (TME). Herein, we report novel CoSn(OH)6@CoOOH hollow carriers with oxidase properties that can enhance phototherapy. Hollow CoSn(OH)6@CoOOH nanocubes (NCs) with a particle size of ∼160 nm were synthesized via a two-step process of coprecipitation and etching. These NCs can react with O2 to generate singlet oxygen without hydrogen peroxide and consume glutathione, and their hollow structure can be utilized to carry drug molecules. After loading indocyanine green (ICG) and 1,2-bis(2-(4,5-dihydro-1H-imidazol-2-yl)propan-2-yl) diazene dihydrochloride (AIPH), the resulting nanosystem (HCIA) exhibited enhanced phototherapy effects through the catalytic activity of oxidase, production of alkyl radicals, and consumption of glutathione. Cell and mouse experiments showed that HCIA combined with near-infrared laser irradiation significantly inhibited the growth of 4T1 tumors. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that PI3K-Akt and MAPK signaling pathways were highly relevant to this therapeutic system. Such hollow NCs with oxidase activity have considerable potential for the design of multifunctional drug delivery vehicles for tumor therapy.

Engineered Red Blood Cell Membrane-Coating Salidroside/Indocyanine Green Nanovesicles for High-Efficiency Hypoxic Targeting Phototherapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) presents special biological behavior and clinicopathological characteristics and leads to a worse prognosis than other types of breast cancer. The development of an effective therapeutic method is significant to improve the survival rate of TNBC cancer patients. In this work, an engineered red blood cell membrane (RBCm)-coating salidroside/indocyanine green nanovesicle (ARISP) is successfully prepared for hypoxic targeting phototherapy of TNBC. Salidroside in ARISP effectively ameliorates hypoxia-induced tumorigenesis by downregulating the expression of hypoxia-inducible factor 1α (HIF-1α), which increases the killing effect of reactive oxygen species on tumor cells during photodynamic therapy (PDT) using the photosensitizer indocyanine green. Besides, ARISP has an anti-LDLR modified RBCm-coating that extends its circulation time in the blood and escapes from immune surveillance and enhances hypoxia-targeted cellular uptake via the overexpressed LDLR receptor in hypoxic tumor sites. Moreover, guided by near-infrared fluorescence imaging and photoacoustic imaging, ARISP can eliminate tumors via high-efficiency phototherapy and inhibit lung and liver metastasis in TNBC models. Cytotoxicity assay of ARISP indicates the excellent biocompatibility with normal cells and tissues. This study provides fulfilling insights into the anticancer mechanism of reducing HIF-1α for enhanced PDT and has a promising therapeutic potential for TNBC treatment.

Role of Doxorubicin on the Loading Efficiency of ICG within Silk Fibroin Nanoparticles.

The effective loading or encapsulation of multimodal theranostic agents within a nanocarrier system plays an important role in the clinical development of cancer therapy. In recent years, the silk fibroin protein-based delivery system has been drawing significant attention to be used in nanomedicines due to its biocompatible and biodegradable nature. In this study, silk fibroin nanoparticles (SNPs) have been synthesized by a novel and cost-effective ultrasonic atomizer-based technique for the first time. The fabricated SNPs were coencapsulated by the FDA-approved indocyanine green (ICG) dye and the chemotherapeutic drug doxorubicin (DOX). The synthesized SNPs are spherical, with an average diameter of ∼37 ± 4 nm, and the ICG-DOX-coencapsulated SNPs (ID-SNPs) have a diameter size of ∼47 ± 6 nm. For the first time, here we demonstrate that DOX helps in the higher loading of ICG within the ID-SNPs, which enhances the encapsulation efficiency of ICG by ∼99%. This could be attributed to the interaction of ICG and DOX molecules with the silk fibroin protein, which helps ICG to get loaded more efficiently within these nanoparticles. The overall finding of this study suggests that the ID-SNPs could be utilized for enhanced ICG-complemented multimodal deep-tissue bioimaging and synergistic chemo-photothermal therapy.

Tumor-triggered targeting ammonium bicarbonate liposomes for tumor multimodal therapy.

Tumor-triggered targeting ammonium bicarbonate (TTABC) liposomes were proposed to improve the uptake of ammonium bicarbonate (ABC) liposomes in tumor cells and retain their long circulation in vivo in our previous study. However, it must be solved how to precisely release the loaded drugs of the TTABC liposomes into tumor cells. In addition, synergistic multimodal therapy could result in better tumor treatment outcomes than monomodal chemotherapy. In the research, we prepared indocyanine green (ICG) and doxorubicin (DOX) encapsulated TTABC liposomes (ICG&DOX@TTABC) to achieve near-infrared (NIR) light-controlled chemo/photothermal/photodynamic multimodal therapy guided by fluorescence and photothermal imaging. In vitro and vivo studies show that ICG&DOX@TTABC can specifically accumulate in tumor tissues, effectively transform NIR light into local thermo-therapy, and have excellent anti-tumor ability without obvious side effects. ICG&DOX@TTABC could be promising for fluorescence and photothermal imaging-guided chemo/photothermal/photodynamic tumor treatment.

Cell-Membrane Biomimetic Indocyanine Green Liposomes for Phototheranostics of Echinococcosis.

Echinococcosis is an important zoonotic infectious disease that seriously affects human health. Conventional diagnosis of echinococcosis relies on the application of large-scale imaging equipment, which is difficult to promote in remote areas. Meanwhile, surgery and chemotherapy for echinococcosis can cause serious trauma and side effects. Thus, the development of simple and effective treatment strategies is of great significance for the diagnosis and treatment of echinococcosis. Herein, we designed a phototheranostic system utilizing neutrophil-membrane-camouflaged indocyanine green liposomes (Lipo-ICG) for active targeting the near-infrared fluorescence diagnosis and photothermal therapy of echinococcosis. The biomimetic Lipo-ICG exhibits a remarkable photo-to-heat converting performance and desirable active-targeting features by the inflammatory chemotaxis of the neutrophil membrane. In-vitro and in-vivo studies reveal that biomimetic Lipo-ICG with high biocompatibility can achieve in-vivo near-infrared fluorescence imaging and phototherapy of echinococcosis in mouse models. Our research is the first to apply bionanomaterials to the phototherapy of echinococcosis, which provides a new standard for the convenient and noninvasive detection and treatment of zoonotic diseases.

A mutually beneficial macrophages-mediated delivery system realizing photo/immune therapy.

The accumulation of nanomedicines in tumor tissues determines their therapeutic efficacy. We herein exploit the tropism of macrophages to improve the accumulation and retention time of nanomedicine at tumors. Interestingly, macrophages are not merely as transporters, but killers activated by nanomedicine. The system(M@C-HA/ICG) was established by decorating macrophages with hyaluronic acid-modified hollow mesoporous carbon (C) nanoparticles loading indocyanine green (ICG). Notably, C nanoparticles with superior photothermal conversion capability not merely guarantee the efficient delivery of ICG through high drug loading efficiency and inhibiting the premature leaky, but effectually activate the polarization of macrophages. The results exhibited that those activated macrophages could release pro-inflammatory cytokines (NO, TNF-α, IL-12), while M@C-HA/ICG afforded about 2-fold higher tumor accumulation compared with pure nanoparticle C-HA/ICG and produced heat and singlet oxygen (1O2) under irradiation of an 808 nm laser, realizing the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and cytokines-mediated immunotherapy. Specially, we also investigated the relationship of singlet oxygen (1O2) or temperature and tumor-killing activity for understanding the specific effectual procedure of PDT/PTT synergistic therapy. Overall, we firstly established an "all active" delivery system integrating the features of nanomedicine with biological functions of macrophages, providing a novel insight for cell-mediated delivery platform and tumor targeted multimodality anti-cancer therapy.

Combined effect of heat shock protein inhibitor geldanamycin and free radicals on photodynamic therapy of prostate cancer.

Prostate cancer is the most common malignancy and the second leading cause of cancer-induced death among men. Recently, photodynamic therapy (PDT) has attracted great attention in prostate cancer treatment because of its high accuracy and no trauma. However, the hypoxic microenvironment of the tumor severely reduces the therapeutic efficacy of oxygen-dependent PDT in prostate cancer, which hampers the generation of reactive oxygen species (ROS). In addition, the PDT process induces the overexpression of pro-survival and anti-apoptotic proteins, thereby reducing the efficacy of PDT. This study proposed a novel multifunctional nanosystem for the targeted delivery of indocyanine green (ICG), 2,2'-azobis[2-(2-imidazolinI-2-yl) propane] dihydrochloride (AIBI), and heat shock protein 90 (Hsp90) inhibitor geldanamycin (17-AAG). Under near-infrared light irradiation, the photothermal effect of ICG induces AIBI decomposition and releases oxygen-independent free radicals, which rescues the hindered ICG-mediated ROS generation. Moreover, 17-AAG reduces heat resistance by inhibiting Hsp90, thereby achieving mild hyperthermia. Simultaneously, the inhibition of Hsp90 can inhibit the overexpression of its client proteins such as anti-apoptotic proteins (survivin) and androgen receptor (AR), thereby improving the efficacy of PDT and inducing prostate cancer cell apoptosis. Results show that the nanosystem enhances PDT by combining free radicals and 17-AAG, exhibiting a good anticancer effect on prostate cancer cells but less toxicity on normal cells.

Polylactide nanoparticles encapsulating indocyanine green for photothermal therapy of prostate cancer cells.

BACKGROUND: The aim of this study is to investigate the in vitro phototherapeutic potential of indocyanine green (ICG) loaded polylactide (PLA) nanoparticles on prostate cancer cells. Many attempts at designing drug delivery systems against cancer were made that incorporates ICG as a photothermal, photodynamic or imaging agent. However, most of these systems contain at least one more drug, making it hard to assess the effects of ICG alone. METHODS: Nanoparticles (ICGNP) were prepared via nanoprecipitation. The effects of phase volume ratio and ICG concentration on size, loading capacity and encapsulation efficiency were explored. Photothermal and photodynamic properties of ICGNP were examined. PC-3 cells were used for cell viability tests. Irradiation was achieved via custom built 809-nm computer controlled diode laser at 1 W/cm2 (up to 600 J/cm2). Data were analyzed by ANOVA followed by Tukey's test (p ≤ 0.05). RESULTS: ICGNP exhibited mean size of 300 nm with low polydispersity, and zeta potential of -14 mV. Upon laser irradiation, ICGNP were capable of causing temperature increase and producing singlet oxygen. On PC-3 cells, ICGNP were proved to be as effective as free ICG in inducing cell death. The measured temperature increase in culture medium and experiments with singlet oxygen quenchers suggest that the decrease in cell viability was mainly the result of photothermal action. CONCLUSIONS: ICGNP was effective as a photothermal agent on PC-3 cells but further improvements are required to increase ICG loading capacity for it to be useful on a wide range of cell types.

Biodegradable mesoporous nanocomposites with dual-targeting function for enhanced anti-tumor therapy.

Tumor-associated macrophages (TAMs), the main components of infiltrating leukocytes in tumors, often play a key role in promoting cancer development and progression. The tumor-specific microenvironment forces the phenotype of tumor-infiltrating to evolve in a direction favorable to tumor development, that is, the generation of M2-like TAMs. Consequently, the dual intervention of cancer cells and tumor microenvironment has become a research hotspot in the field of tumor immunotherapy. In this contribution, we developed pH-sensitive mesoporous calcium silicate nanocomposites (MCNs) encapsulated with indocyanine green (ICG) to enable the effective combination of photothermal therapy (PTT) and photodynamic therapy (PDT) triggered by the 808 nm near-infrared (NIR) light. The mannose and hyaluronic acid-grafted MCNs specifically targeted TAMs and tumor cells and promoted cell apoptosis both in vitro and in vivo. This paper revealed that irradiation of ICG loaded MCNs with NIR can produce a potent hyperthermia and induce abundant intracellular singlet oxygen generation in the target cells. These results suggest that the novel nanoplatform is believed to facilitate the delivery of chemotherapeutic agents to the tumor microenvironment (TME) to enhance the effects of tumor treatment.

Second near-infrared photothermal-amplified immunotherapy using photoactivatable composite nanostimulators.

BACKGROUND: The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response. RESULTS: Here, a composite nanostimulator (CNS) was constructed for the release of second near-infrared (NIR-II) photothermal-mediated immune agents, thereby achieving spatiotemporally controllable photothermal-synergized immunotherapy. CNS nanoparticles comprise thermosensitive liposomes as an outer shell and are internally loaded with a NIR-II photothermal agent, copper sulfide (CuS), toll-like receptor-9 (TLR-9) agonist, cytosine-phospho-guanine oligodeoxynucleotides, and programmed death-ligand 1 (PD-L1) inhibitors (JQ1). Following NIR-II photoirradiation, CuS enabled the rapid elevation of localized temperature, achieving tumor ablation and induction of immunogenic cell death (ICD) as well as disruption of the lipid shell, enabling the precise release of two immune-therapeutical drugs in the tumor region. Combining ICD, TLR-9 stimulation, and inhibited expression of PD-L1 allows the subsequent enhancement of dendritic cell maturation and increases infiltration of cytotoxic T lymphocytes, facilitating regional antitumor immune responses. CONCLUSION: CNS nanoparticle-mediated photothermal-synergized immunotherapy efficiently suppressed the growth of primary and distant tumors in two mouse models and prevented pulmonary metastasis. This study thus provides a novel sight into photo-controllably safe and efficient immunotherapy.

Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy.

BACKGROUND: Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. RESULTS: Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. CONCLUSIONS: Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.

"Stealth" dendrimers with encapsulation of indocyanine green for photothermal and photodynamic therapy of cancer.

Poly(amido amine) dendrimers and indocyanine green have inevitable interaction with proteins and cells, which induces biological toxicity and reduces therapeutic efficacy in vivo. To overcome these shortcomings, a new drug delivery system G5MEK7C(n)-ICG with a "stealth" layer was prepared. The surface of G5MEK7C(n)-ICG was modified with double-layer super hydrophilic zwitterionic materials. In the "stealth" double-layer structure, the outer layer was consisted of zwitterionic Glu-Lys-Glu-Lys-Glu-Lys-Cys (EK7) peptide, and the inner layer was composed of amino and carboxyl groups with a ratio of 1:1. DLS results showed that the average hydrodynamic size of G5MEK7C(n)-ICG was about 25-30 nm, and the zeta potential was proven to undergo a slight charge reversal with the increasing pH values of solutions. Furthermore, G5MEK7C(n)-ICG exhibited excellent biocompatibility to red blood cells and proteins resistance. Photothermal and photodynamic experiments demonstrated that G5MEK7C(n)-ICG had a good photothermal conversion effect and generated singlet oxygen (1O2) under laser irradiation. The MTT and hemolysis results showed that the toxicity of G5 PAMAM was significantly reduced after modification double-layer structure. Cytotoxicity studies and flow cytometry showed G5MEK7C(70)-ICG under laser irradiation had a good effect on killing A549 cells. More importantly, the tumor inhibition rate of mice treated with G5MEK7C(70)-ICG (under laser irradiation) was 78.2% in vivo, which was higher than that of mice treated with free ICG. Compared with free ICG, G5MEK7C(70)-ICG caused less damage to the liver according to the enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Therefore, dendrimers modified with a zwitterionic double layer will be a promising candidate as a drug delivery system.