Chemo-photothermal Synergistic Cancer Therapy Research Articles

The collaborated assembly of hydrophobic curcumin and hydrophilic cyanine dye into nanocolloid for synergistic chemo-photothermal cancer therapy

Carrier-free nanomedicine represents a new opportunity of using less inert materials for efficient drug delivery. To date, most reported carrier-free nanomedicine systems rely heavily on π-π stacking interaction between hydrophobic drugs. This work found that the hydrophilic IR783 dye can collaborate with the hydrophobic curcumin (Cur) compound to form a novel Cur@IR783 nanocolloid (NC) via self-assembly. The self-assembly of the hydrophilic IR783 and hydrophobic Cur improved the water dispersity of Cur, significantly facilitating its administration in vivo. Moreover, Cur@IR783 NC retained the IR783 properties of NIR fluorescence and photothermal conversion efficiency. Fluorescence imaging demonstrated that Cur@IR783 NC accumulated at the tumor site via the enhanced permeation and retention effect, which ensured enhanced anti-tumor effect. In vitro and in vivo experiments showed that the Cur@IR783 NC with laser irradiation yielded the most potent antitumor effect, and Cur@IR783 NC exhibited high biocompatibility. Overall, Cur@IR783 NC showed remarkable synergistic antitumor activity via chemo-photothermal combination therapy, providing a new promising approach for Cur-based applications in cancer treatment.

Fabrication of BiCuOS nanoflowers acting as nanoarrays on photonic nanoparticles for chemo-photothermal therapy

In recent years, 3D flower shaped nanostructures with an ability to improve internal photo reflections and absorptions is gaining popularity for the development of photo-thermal heat generating materials for cancer therapy. The use of bimetallic oxysulfide materials as photo-thermal agent is especially interesting as it is not only resulting in heat generation by absorbing laser light in the biological window but also participates in reactive oxygen species generation in tumor environment. In this work, we have reported a novel flower shaped BiCuOS nanostructures made of CuS base structures with vertical nanoarrays of bismuth oxide nanoplates for synergistic chemo-photothermal cancer therapy. Notably, 2D nanoplates (∼150 ± 50 nm in length and thickness of about ∼25 nm) could be seen grown in the form of nanoflowers (NFs) of 800 ± 100 nm in size on CuS base structures. The electronic structure, density of states, bond angle, bond length and thermal stability of formed NFs were investigated by density functional theory and molecular dynamic studies. The photo-thermal conversion efficiency was increased as a function of NF concentration. The percentage of doxorubicin released was estimated to be only ∼4% even after one day of incubation at pH 7.4 which increased to 38 and 45% at pH 5.5 without and with near infra-red light exposure, respectively. The cell viability experiments with fibroblast cells and red blood cells exhibited excellent biocompatibility of BiCuOS NFs. The synthesized BiCuOS NFs showed excellent anticancer activity against Hep-2 cells. Hence, the BiCuOS NFs reported here have huge potential for use as novel dual performing chemo-and-photothermal agent for advanced cancer therapy.

Hollow carbon nanospheres loaded with upconversion nanoparticles for chemo-photothermal synergistic cancer therapy

Hollow carbon nanospheres loaded with upconversion nanoparticles for chemo-photothermal synergistic cancer therapy

A Smart Benzothiazole-Based Conjugated Polymer Nanoplatform with Multistimuli Response for Enhanced Synergistic Chemo-Photothermal Cancer Therapy

The combination of chemotherapy and phototherapy has received tremendous attention in multimodal cancer therapy. However, satisfactory therapeutic outcomes of chemo-photothermal therapy (chemo-PTT) still remain challenging. Herein, a biocompatible smart nanoplatform based on benzothiazole-linked conjugated polymer nanoparticles (CPNs) is rationally designed, for effectively loading doxorubicin (DOX) and Mo-based polyoxometalate (POM) through both dynamic chemical bond and intermolecular interactions, with an expectation to obtain new anticancer drugs with multiple stimulated responses to the tumor microenvironment (TME) and external laser irradiation. Controlled drug release of DOX from the obtained nanoformulation (CPNs-DOX-PEG-cRGD-BSA@POM) triggered by both endogenous stimulations (GSH and low pH) and exogenous laser irradiation has been well demonstrated by pharmacodynamics investigations. More intriguingly, incorporating POM into the nanoplatform not only enables the nanomedicine to achieve mild hyperthermia but also makes it exhibit self-assembly behavior in acidic TME, producing enhanced tumor retention. Benefiting from the versatile functions, the prepared CPNs-DOX-PEG-cRGD-BSA@POM exhibited excellent tumor targeting and therapeutic effects in murine xenografted models, showing great potential in practical cancer therapy.

A pH/temperature responsive nanocomposite for chemo-photothermal synergistic cancer therapy

To optimize synergistic breast cancer treatment, a nanocomposite was fabricated with pH-temperature responsive and chemo-photothermal combination therapy. Herein, gold nanorods (AuNRs) are coated with [poly[(N-isopropylacrylamide)-co-(methacrylic acid)] (p(NIPAM-co-MAA)) modified mesoporous silica (MS) for Doxorubicin (DOX) delivery (AuNR@DOX-MS@p(NIPAM-co-MAA)). Upon NIR radiation, the AuNR core induced hyperthermia via generating heat. Simultaneously, the polymer layer collapsed in response to high temperature/low pH, which allowed the triggering of DOX release from the MS shell at the tumor site. With this nanocomposite, nearly zero premature release of DOX at physiological pH/temperature was detected, while effective DOX release was reported at higher temperature/lower pH values. In addition, in vitro studies demonstrated that the nanocomposite has a substantial uptake efficiency of MDA-MB-231 breast cancer cells, with a significant increase in suppressing MDA-MB-231 ​cell proliferation in response to laser irradiation. The in vivo experiments further verified the high efficiency of the fabricated nanocomposite in accumulating at the tumor site and the good capability in suppressing tumor growth in the mice upon intravenous injection, while exhibiting good biosafety in relation to major organs in the body. Thus, the synthesized nanocomposite could be a potential nanocarrier for breast cancer treatment with synergistic chemo-photothermal therapeutic capability.

NIR light-powered halloysite-based nanomotors for CT imaging diagnosis and synergistic chemo-photothermal cancer therapy

Near-infrared (NIR) light-powered nanomotors with active motion have attracted extensive attention in the chemo-photothermal therapy of cancer. However, there are also some limitations such as complicated synthesis process, low permeability of drugs and viscous physiological environment. Herein, we developed a facile route to synthesize novel NIR light-powered DOX/Au-m-HTAS nanomotor based on natural halloysite (HNTs) for active chemo-photothermal therapy. Such nanomotor exhibited NIR light controlled on/off motion with a maximum speed of 64.5 μm/s. Owing to the synergetic NIR light-powered motion and chemo-photothermal therapy, DOX/Au-m-HTAS nanomotor could effectively adhere tumor cells, leading to deeper cell penetration, higher cellular uptake, and better ablation of tumor cells. Meanwhile, DOX/Au-m-HTAS nanomotors also had enhanced ability for CT imaging of local tumor, demonstrating the enhanced anticancer efficiency. This strategy provided a new insight into the chemo-photothermal synergistic therapy of tumors.

Development of ligand modified erythrocyte coated polydopamine nanomedicine to codeliver chemotherapeutic agent and oxygen for chemo-photothermal synergistic cancer therapy

The use of conventional chemotherapy often faces limitations such as severe side effects, weak tumor tissue specificity, and the development of multidrug resistance. To conquer these challenges, numerous novel drug carriers have been designed in recent years. However, due to the complex processes of tumor development, metastasis and recurrence, single chemotherapy cannot fulfill the goals of clinical diverse treatment. In this work, by utilizing the inherent characteristics of surface-modified erythrocyte and the outstanding photothermal conversion capability of polydopamine (PDA), we designed and constructed a biomimetic multifunctional nanomedicine DPPR NPs to codeliver chemotherapeutic agent doxorubicin (DOX) and oxygen. The results showed that DPPR NPs exhibited inspiring features including nanoscale droplet size, good physicochemical stability, and sustained, pH-, and NIR triggered drug release behavior. It can dramatically prolong the systematic circulation time and elevated the drug accumulated level in the tumor site. Moreover, DPPR NPs could be effectively internalized into tumor cells and destroyed the intracellular redox balance to mediate cell apoptosis. It exerted excellent in vivo tumor targeting effect, photothermal conversion efficiency, ultrasound imaging responses, antitumor efficacy, and good compatibility. In summary, DPPR NPs provide a biomimetic drug delivery platform to organically combine chemotherapy and photothermal therapy for precise cancer treatment.

Hybrid micelles loaded with chemotherapeutic drug-photothermal agent realizing chemo-photothermal synergistic cancer therapy

The synergistic therapy of malignant tumors with chemotherapy and photothermal therapy has attracted extensive researcher attention. With the further development of photosensitizers, photosensitizer delivery and stability are the urgent problem to be solved at present. In this study, the biodegradable hybrid micelles (HMs) nano system for co-delivery paclitaxel (PTX) and IR825, investigating the photosensitizer stability in the drug delivery system and therapeutic effectiveness in vitro or in vivo. The hybrid micelle (PTX/IR825-TAT HMs) was self-assembled through hydrophobic interactions between polyethyleneimine-polycaprolactone (PEI-PCL) and TAT peptide modifided-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)5000 (TAT-PEG-DSPE). The results indicated that TAT HMs could successfully encapsulate IR825 PTX (PTX/IR825-TAT HMs). More importantly, IR825 encapsulated in hybrid micelles improved physiological stability, thermostability and photostability. In addition, the PTX released rapidly from PTX/IR825-TAT HMs in acidic and laser irradiation environments. In vitro cell analysis demonstrated that PTX/IR825-TAT HMs exhibited effective internalization of breast cancer cells. At the same time, PTX/IR825-TAT HMs with laser irradiation synergistically induced cancer cell apoptosis and death. indicating chemo-photothermal therapy synergistic therapeutic effect. In vivo antitumor studies showed that PTX/IR825-TAT HMs precisely reached the tumor tissue and convert light energy into heat energy under laser irradiation, PTX/IR825-TAT HMs had excellent synergistic antitumor efficiency compared to single chemotherapy and photothermal therapy.

Biodegradable 2D GeP nanosheets with high photothermal conversion efficiency for multimodal cancer theranostics

• Discovery of a new indirect bandgap phosphorus-based 2 D materials with a super photothermal conversion efficiency of 68.6 %. • Multimodal-imaging-Guided drug delivery of GeP nanosheets based platform for cancer. • GeP nanosheets based platform with excellent biodegradation and biocompatibility. • Stimulative responsive drug releasing and tumor inhibition of the GeP nanosheets based hybrid platform. Germanium phosphide (GeP), a new member of phosphorus-based 2D materials, is a semiconductor with indirect and narrowed band gap, which theoretically would have great potential to serve as near-infrared (NIR) photothermal agent (PTA) with high photothermal conversion efficiency (PTCE). However, the photothermal conversion performance and biomedical application of GeP-based nanocarriers has not been explored yet. Herein, we demonstrate the GeP nanosheets as high-performance PTA with PTCE of 68.6% in NIR region, which is much higher than many of other 2D PTA such as graphene, Mxenes, transition metal dichalcogenides, and black phosphorus (BP), and explore its application in multimodal cancer theranostics. Similar to BP nanosheets, the GeP nanosheets are biodegradable with excellent biocompatibility. With the merit of large specific surface area, the GeP nanosheets have high loading capacity (134 wt%) for anticancer drug Doxorubicin (DOX). The NH 2 -PEG-FA modified GeP-DOX hybrids show pH-responsive, heat-stimulative and sustained-drug-release performance as chemo-photothermal synergistic cancer therapy platform, and demonstrate remarkable tumor ablation ability both in vitro and in vivo . Meanwhile, multimodal imaging capability including photoacoustic imaging and photothermal imaging is also realized on basis of the excellent photothermal performance of GeP nanosheets. This study highlights the great promise of 2D GeP nanosheets as multifunctional platform for cancer theranostics application.

Synergistic chemo-photothermal cancer therapy of pH-responsive polymeric nanoparticles loaded IR825 and DTX with charge-reversal property

IR825 is a kind of near-infrared (NIR) small molecule cyanine dye and has distinct near-infrared absorbance and excellent thermal conversion performance. Due to poor stability and insufficient therapy efficacy, various nano-systems have been developed as delivery vehicles for NIR dyes to improve their application in tumor treatment. Herein, we developed an intelligent polymer drug vehicle (Mal-PAH-PEG-DMMA/ poly (ethylene imine) – poly(ε-caprolactone) block polymers, MPPD/PEI-PCL) based on pH-responsive charge-reversal to deliver docetaxel (DTX) and photosensitizer (IR825) for chemo-photothermal combination therapy (MPPD@IR825/DTX NPs). MPPD@IR825/DTX NPs could undergo charge conversion in a slightly acidic microenvironment (pH 6.8), resulted in strong electrostatic repulsion to withdraw the shell of the polymer nanoparticles (MPPD), enhanced cellular uptake and increased drug release. MPPD@IR825/DTX NPs demonstrated nanoscale in size with good mono-dispersity and stability, triggered DTX release in response to acid environment and NIR stimulation, in the same time providing excellent photothermal conversion efficiency. In vitro and In vivo experiments confirmed that charge-reversal polymeric nanoparticles improved antitumor efficiency in 4T1 tumor cell modal than non-charge-reversal polymeric nanoparticles. Furthermore, in comparison with chemotherapy or photothermal therapy in a single treatment mode, chemo-photothermal combination therapy of MPPD@IR825/DTX NPs with laser irradiation showed highly efficient tumor ablation. In addition, the polymeric nanoparticles exhibited good biocompatibility and safety. Therefore, the design of charge-reversal polymeric nanoparticles (MPPD@IR825/DTX NPs) provides a new strategy and promising application for targeting and synergistic chemo-photothermal combination therapy.

Capsule-like molecular imprinted polymer nanoparticles for targeted and chemophotothermal synergistic cancer therapy

Selective cancer cell targeting, controlled drug release, easy construction and multiple therapeutic modalities are some of the desirable characteristics of drug delivery systems. We designed and built simple capsule-like molecular imprinted polymer (MIP)-based nanoparticles for targeted and chemo-photothermal synergistic cancer therapy. Using dopamine (DA) as functional monomer, cross-linking agent as well as photo-thermal agent, ZIF-8 (zeoliticimidazolate framework-8) as drug carrier, epitope of EGFR (epidermal growth factor receptor) as template molecules, molecular imprinted polymer (MIP) drug carrier was constructed. The ability of MIP layer to bind to EGFR epitope endowed the MD (DOX@MIP) particles to recognize EGFR-overexpressing cancer cells, while the pH-responsiveness and photothermal conversion ability of PDA (polydopamine) achieved chemo-photothermal synergistic effects upon NIR irradiation. Taken together, the MD nanoparticles integrated cancer cell targeting recognition, intelligent drug release, biocompatibility and chemo-photothermal effects, and is therefore a promising tool for targeted cancer therapy with minimal toxicity to normal cells, as well as tumor imaging.

Nanogold-loaded chitosan nanocomposites for pH/light-responsive drug release and synergistic chemo-photothermal cancer therapy

Stable and biocompatible nano-agents that stimulate the combined cancer therapy are of great necessity. Herein, a ternary system composed of optimally prepared chitosan nanoparticles (ChNPs) efficiently encapsulating 5-Fluorouracil (5-FU) and loaded by gold nanoparticles (AuNPs) was employed for synergistic chemo-photothermal therapy. The composed 5-FU-ChNPs@Au nanocomposites (NCs) combine the features of ChNPs, 5-FU, and AuNPs and exhibit excellent biocompatibility, stability, and killing efficiency of tumor cells. Moreover, its strong absorbance in the visible region promotes the fast release of drug under laser exposure. The synergistic effect of 5-FU-ChNPs@Au was demonstrated in comparison to a variant system (5-FU-ChNPs) which was prepared devoid of AuNPs. The dynamic light scattering of the synthesized NCs verified the high stability and homogeneity of particle size distribution. Cytotoxicity experiments towards hepatocellular carcinoma cells (HepG2) revealed that the combined chemo-photothermal therapy of 5-FU-ChNPs@Au featured highly synergistic manner. These findings offer the 5-FU-ChNPs@Au NCs as a highly potential chemo-photothermal therapeutic platform.

Folic Acid-Modified Erythrocyte Membrane Loading Dual Drug for Targeted and Chemo-Photothermal Synergistic Cancer Therapy.

To overcome the challenges of systemic toxicity and weak tumor selectivity caused by traditional antitumor drugs, numerous nanocarrier systems have been developed in recent decades, and their therapeutic effect has been improved to varying degrees. However, because of the drug resistance effect and metastasis involved in tumor recurrence, a single chemotherapy can no longer satisfy the diversified treatment needs. Recently, the application of chemotherapy in combination with thermotherapy as a synergistic approach has been proven to be more effective, and it provides a new strategy for cancer therapy. In this work, by utilizing the unique properties of erythrocytes, a surface-modified erythrocyte membrane was constructed as a novel nanocarrier system (DOX and ICG-PLGA@RBC nanoparticles, DIRNPs for short) for the simultaneous transportation of chemotherapeutic drugs (doxorubicin, DOX) and photothermal agents (indocyanine green, ICG) to achieve the effects of long-term circulation, active tumor targeting, and triggered drug release. The results indicated that DIRNPs have a nanoscale particle size of 158.4 nm with a narrow size distribution and a negative surface charge of -5.79 mV. No particle aggregation or remarkable drug leakage was observed during the 30 day storage test, and because of the excellent photothermal conversion ability of ICG, the local temperature of DIRNPs could dramatically increase from 33.7 to 49.8 °C in 10 min under near-infrared (NIR) laser irradiation. The in vitro drug dissolution data demonstrated that the DOX release from the DIRNPs was pH-dependent and NIR-triggered. Folic acid modifications of the erythrocyte membrane effectively facilitated the intracellular uptake of DIRNPs by HepG2 cells and, as a result, it significantly inhibited tumor cell growth, promoted reactive oxygen species levels, induced cell apoptosis, and restricted cell recovery and migration. In vivo pharmacokinetics and biodistribution studies indicated that the DIRNPs prolonged the half-life of DOX from 6.03 to 17.6 h and remarkably reduced the DOX level in the heart to avoid drug-related cardiotoxicity. More importantly, the DIRNPs exerted excellent in vivo antitumor efficacy against H22 tumors with superior safety. In conclusion, utilizing the advantageous properties of erythrocytes to construct a tumor-targeted biomimetic nanocarrier for codelivery of chemotherapeutics and photothermal agents to produce synergistic effects is considered an effective method for cancer therapy.

Black phosphorus nanosheets-based platform for targeted chemo-photothermal synergistic cancer therapy

As a new member of two-dimensional (2D) nanomaterials, black phosphorus (BP) has been considered as efficient photothermal therapy (PTT) agents owing to its excellent photothermal efficiency and biodegradability. Herein, a multifunctional nanoplatform based on black phosphorus nanosheets (BP NSs) was developed for chemo-photothermal synergistic cancer therapy. The BP NSs were successfully prepared by a liquid exfoliation technique. Doxorubicin (DOX), as a model drug, was loaded into the cavity of poly (amidoamine) (PAMAM) dendrimer using thin film hydration method. Then, PAMAM@DOX was coated on the surface of BP NSs using an electrostatic adsorption method that combined bath sonication with magnetic stirring. Hyaluronic acid (HA) was also modified onto the BP NS-PAMAM@DOX through electrostatic adsorption. PAMAM and HA layer could effectively isolate BP NSs from water and air to improve physiological stability. BP NSs and BP NS-PAMAM@DOX-HA were characterized by particle size, zeta potential, morphology, UV–vis-NIR absorption spectra, stability, photothermal performance and photothermal stability. This nanosystem exhibited a good pH and near infrared (NIR) dual-responsive drug release property. In addition, the obtained BP NS-PAMAM@D OX-HA nanocomposites possessed excellent PTT efficiency both in vitro and in vivo. The in vitro cell experiments suggested that the targeted BP NS-PAMAM@DOX-HA presented greater cytotoxicity and higher cellular uptake efficiency. Tumor xenograft model was established in BALB/C mice. The therapeutic effect of BP NS-PAMAM@DOX-HA was further augmented under 808 nm laser irradiation, displaying superior antitumor effect in comparison with chemotherapy or PTT alone. Such a biodegradable BP NS-based platform provide new insights for the rational design of PTT-based combinational cancer therapy.

Hollow Mesoporous Bi@PEG-FA Nanoshell as a Novel Dual-Stimuli-Responsive Nanocarrier for Synergistic Chemo-Photothermal Cancer Therapy.

The development of stimuli-responsive multifunctional nanocarriers for therapeutic drug delivery is extremely desirable for highly specific treatment of disease. Herein, thiol-polyethylene glycol-folate acid-modified hollow mesoporous bismuth nanoshells (HM-Bi@PEG-FA NSs) were developed as the new dual-stimuli-responsive single-"elemental" photothermal nanocarriers for synergistic chemo-photothermal therapy of tumor. The designed hollow-mesoporous-type nanocarriers present excellent photothermal conversion capacity (∼34.72%) and good biocompatibility. Meanwhile, acidic pH and near-infrared (NIR) laser dual-stimulated doxorubicin (DOX) release is successfully achieved. More importantly, the DOX-loaded HM-Bi@PEG-FA NSs hold an efficient in vitro/in vivo antitumor effect through the synergistic chemo-photothermal therapy. Therefore, our findings provide the possibility of designing a dual-stimuli-responsive hollow mesoporous Bi-based photothermal nanocarrier for synergistically enhanced antitumor therapy.

Self-Assembly Nanoparticles for Overcoming Multidrug Resistance and Imaging-Guided Chemo-Photothermal Synergistic Cancer Therapy.

Background and PurposeThe development of multiple drug resistance (MDR) to chemotherapy and single modal therapy remains unsatisfied for the eradication of tumor, which are major obstacles in cancer therapy. This novel system with excellent characteristics for inhibition of P-glycoprotein (P-gp), and for near-infrared fluorescence (NIRF) imaging-guided chemo-photothermal therapy (PTT), has been identified as a promising way to MDR and achieve synergistic cancer therapy.MethodsIn this study, we successfully synthesized a multifunctional theranostic system, which was developed through FDA-approved self-assembling drugs, which contain anticancer drug doxorubicin (Dox), imaging and high photothermal conversion drug indocyanine green (ICG) and P-gp regulator TPGS (the system named T/Dox-ICG). We studied the characterization of T/Dox-ICG NPs, including the TEM, SEM, DLS, UV-vis-NIR, zeta potential, CLSM, in vitro FL imaging, in vitro photothermal effect, in vitro Dox and ICG release. We used CLSM to verify the location of intracellular distribution of Dox in SCG 7901/VCR cells, Western blot was performed to demonstrate the TPGS-mediated inhibition of P-gp. And, the cytotoxicity of materials against SCG 7901/VCR cells was studied by the MTT assay.ResultsThe TEM showed the T/Dox-ICG NPs had good monodispersity with diameters of 19.03 nm, Dox and ICG could be released constantly from T/Dox-ICG NPs in vitro. In vitro cell experiments demonstrated higher Dox accumulation and retention in the nucleus. Western blot showed TPGS could obviously inhibit the expression of P-gp. In vitro cytotoxicity assay showed more significant cytotoxicity on MDR cells (SCG 7901/VCR) with only 8.75% of cells surviving.ConclusionMDR cancer therapy indicates that it may be important to develop a safer system that can simultaneously inhibit the drug transporters and monitor the delivery of chemotherapeutic agents, and combination therapy have raised widespread concern on tumor treatment.

Multifunctional hierarchical mesoporous silica and black phosphorus nanohybrids as chemo-photothermal synergistic agents for enhanced cancer therapy.

Synergistic therapy with high efficacy and low side effects is of great significance in cancer treatment, and therefore the elaborate design of advanced nanocarriers to benefit diverse loading requirements of size-varied therapy agents is of critical importance. Herein, we demonstrate a multifunctional drug carrier platform based on a hierarchical porous and -NH2-modified silica nanocarrier (FMSN) with a super high specific surface area and a large pore volume, which not only improves the loading capacity of both doxorubicin, a chemotherapeutic drug, and black phosphorus quantum dots (BPQDs), a kind of biocompatible photothermal agent, but also enhances the photothermal stability and biostability of the degradable BPQDs. The unique structure and surface design enable our multimodal platform with heat-stimulative, pH-responsive and sustained-release properties for chemo-photothermal synergistic cancer therapy. Both cytotoxicity experiments and in vivo study reveal that the combined therapy based on our multifunctional nanohybrids mediates the highest death rate of cancer cells compared to that of single chemotherapy or photothermal therapy. Our hierarchical mesoporous strategy provides an excellent drug delivery model for advanced chemo-photothermal synergistic targeted cancer therapy.

Multistage-Targeted Gold/Mesoporous Silica Nanocomposite Hydrogel as In Situ Injectable Drug Release System for Chemophotothermal Synergistic Cancer Therapy

Injected tissue-affinity drug-laden nanocomposite hydrogels are promising materials for tumor therapy owing to both maintenance and release of drug in situ. In this study, a hyaluronic acid (HA) hydrogel covalently embedded with doxorubicin loaded and triphenylphosphine (TPP) modified core-shell gold mesoporous silica nanoparticles is fabricated as a local drug-delivery system for sustained stomach cancer treatment. HA has excellent biocompatibility as the main component of the extracellular matrix and specific affinity toward the CD44-overexpressed cancer cell. TPP is a classic targeted feature of mitochondria. After in situ injection, the hydrogel patch can adhesively land at the tumor site, and it exerts further control through dissociation because of the degradation of hyaluronidase around the solid tumor, leading to the release of core-shell gold mesoporous silica nanoparticles conjugated with TPP and HA fragment. These particles can selectively attack cancer cells followed by entering into mitochondria. Additionally, the core gold nanoparticle mediates the transformation of near-infrared radiation into thermal energy, enhancing the release of chemotherapy drugs and heat-induced cellular injury. This in situ, chemophotothermal combination hydrogel is verified to have an excellent therapeutic effect on gastric tumor through in vitro and in vivo experiments, providing the potential to serve as a multistage-target drug-delivery platform for chemophotothermal synergistic cancer therapy.

Facile synthesis and characterization of multifunctional cobalt-based nanocomposites for targeted chemo-photothermal synergistic cancer therapy

In this study, we develop polyethylene glycol (PEG) modified nanocomposites, which structurally constitute graphene oxide (GO) and cobalt nanoparticles (CoNPs), called as the CoNPs-GO-PEG nanocomposites. These CoNPs-GO-PEG nanocomposites show better outcomes and less side effects when eliminating tumor cells. After a series of comprehensive characterizations, the CoNPs-GO-PEG nanocomposites are proved to possess pleasing targeting ability and unique drug release behavior, indicating that the concentration of the drug delivered by CoNPs-GO-PEG in the tumor site is much higher than that in the normal tissue, and concerning the favorable biocompatibility of CoNPs-GO-PEG nanocomposites, less harm is caused to normal tissue compared to traditional chemotherapy. Furthermore, because of the satisfactory photothermal effect and favorable drug release behavior of the material, the CoNPs-GO-PEG are able to eradicate most of the tumor cells (99%) through synergistic chemo-photothermal therapy in vitro. So far, our study has demonstrated an inspiring potential for the CoNPs-GO-PEG nanocomposites to act as a favorable targeting multifunctional agent in cancer therapy.

Laser-Triggered Injectable Gelatin Hydrogels System for Combinatorial Upconversion Fluorescence Imaging and Antitumor Chemophotothermal Therapy.

Diagnosis and multitherapy strategies that coexist in a single system for cancer therapy has a great clinical application potential. In this paper, we developed doxorubicin (DOX)-loaded gelatin hydrogels contained with UCNP@NGO nanoparticles (Gelatin/UCNP@NGO+DOX) for chemophotothermal dual-model synergistic cancer therapy and upconversion luminescence (UCL) imaging. Gelatin/UCNP@NGO+DOX hydrogels could release the DOX via laser irradiation or in tumor microenvironment, and then cancer therapy efficiency could be improved by chemophotothermal synergistic effects. In vitro experimental Gelatin/UCNP@NGO+DOX hydrogels exhibit outstanding photothermal properties and excellent tumor-killing efficiency. We also use in vivo antitumor experiments to further illustrate that Gelatin/UCNP@NGO+DOX hydrogels can exhibit excellent synergistic antitumor efficacy, compared with chemotherapy or photothermal methods. This paper shows a new hydrogel system that could both load chemotherapeutic drugs efficiently and enhance chemotherapy effect using near-infrared light-radiation photothermal therapy.