Synergistic Chemo-photothermal Therapy Research Articles

Two-dimensional MXene-based nano-prodrug for synergistic chemo-photothermal therapy on cancer treatment

In cancer treatment, although prodrugs have been developed to overcome obstacles such as undesirable pharmacokinetic performance and serious off-target toxicity of most chemotherapeutics, the combination of prodrugs with nanotechnology could be used to overcome the shortcomings of conventional prodrug strategies and facilitate more efficient drug delivery and accumulation of anticancer prodrugs at specific sites/tissues. Phototherapy is a method that uses near-infrared (NIR) light to achieve local and non-invasive tumor therapy. The combination of chemotherapy and phototherapy has shown many therapeutic advantages, including synergistic therapeutic effects and the reduction of toxic and side effects of drugs through dose reduction. In this work, a hydrazone linkage was reported to conjugate Ti3C2Tx MXene nanosheets with doxorubicin hydrochloride (DOX) and methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) through a chemical surface modification to form a two-dimensional (2D) nano-prodrug Ti3C2Tx-DOX/PEG (TDP) for synergistic chemo-photothermal therapy. First, hydrazide functionalized Ti3C2Tx was obtained. Then, the carbonyl group of DOX and the aldehyde group of mPEG-CHO can form a pH-responsive hydrazone bond with hydrazide-functionalized Ti3C2Tx. The high surface area of Ti3C2Tx could overcome the reduced drug loading caused by conjugation. Aqueous stability and biocompatibility were enhanced by the introduction of PEG, making the material capable of prolonged circulation in the body’s bloodstream. By achieving excellent antitumor results with this nano-prodrug, we have added another brick to the edifice of Ti3C2Tx MXene as an anticancer drug carrier, and given new vitality to the study of anticancer prodrugs combined with nanotechnology.

A targeting multiple-stimuli responsive POSS-based smart nanomaterial for enhanced chemo-photothermal synergistic therapy

The combination of chemotherapy and photothermal therapy has garnered significant attention in the field of multimodal cancer therapy. However, achieving precise and controllable delivery of therapeutic agents remains a challenge. In this study, we designed a biocompatible smart nanomaterial (PSD-FA) for efficient loading of doxorubicin (DOX) through dynamic chemical bonding, with the aim of achieving responsive behavior to both the tumor microenvironment (TME) and external laser irradiation. The incorporation of PEG into the nanoplatform enhanced hydrophilicity of PSD-FA NPs. Folic acid (FA) served as a targeting ligand to guide the nanoparticles tumor sites. On one hand, SQ-N acted as an effective photothermal agent that efficiently converted light energy into heat energy upon stimulation by exogenous near-infrared light. This localized increase in temperature at the tumor site facilitated targeted killing of tumor cells. On the other hand, after photothermal therapy-induced tumor ablation, DOX was released in response to redox stimuli due to significantly higher concentrations of glutathione (GSH), an antioxidant presents in TME. This allowed deep penetration into the tumor tissue, expanding the attack area and inhibiting nucleic acid synthesis in tumor cells, ultimately leading to cell death. Both in vitro and in vivo experiments demonstrated excellent anticancer efficacy of PSD-FA NPs. Overall, this intelligent nanomaterial successfully achieved targeted drug delivery with redox-responsive release capabilities while synergistically combining chemo-photothermal therapies, thus exhibiting great potential for clinical applications.

Propolis polyphenol nanosheet for synergistic cancer chemo-photothermal therapy

Two-dimensional (2D) carbon-based nanostructures hold great promise as near-infrared (NIR) photothermal materials, yet their widespread use has been hindered by labor-intensive and costly fabrication processes. Here, a novel, cost-effective approach is presented to produce photothermal materials derived from the polyphenolic fraction of propolis (PFP) for the first time. The method involves the pyrolysis of PFP under a neutral atmosphere, resulting in the formation of 2D PFP-based nanosheets (PFPNS) measuring 50–100 nm in size with efficient photothermal properties. Then, a layer-by-layer nanohybrid structure comprising PFPNS, polydopamine (PDA), mesoporous silica (MS), and polyethyleneimine (PEI) layers (PFPNS@PDA@MS-PEI) was designed as a versatile platform for drug delivery. Specifically, the anticancer drug doxorubicin (DOX) was loaded onto the nanohybrid (PFPNS@PDA@MS(DOX)-PEI) for targeted delivery to cancerous cells. Each layer of the nanohybrid serves a distinct purpose, enhancing functionality and efficacy. The NIR-responsive PFPNS@PDA component facilitates accelerated drug release and induces hyperthermic effects on cancer cells upon NIR irradiation. The MS structure enables high drug loading capacity (approximately 83.3%), while the pH-responsive PEI layer promotes cellular uptake and facilitates drug release within the acidic microenvironment of cancer cells. Combining NIR irradiation with chemotherapy results in a synergistic effect, leading to the eradication of 67% of MCF-7 breast cancer cells. The demonstrated efficacy, coupled with the non-toxic nature of the nanohybrid, positions it as a promising candidate for synergistic chemo-photothermal therapy of tumor tissues.

Spherical g-C3N4@PDA nanocarrier for synergistic chemo-photothermal tumor therapy

In this paper, by wrapping the near-infrared (NIR) response polydopamine (PDA) as a nanocoating on the surface of spherical nano graphitic phase carbon nitride (g-C3N4), a multifunctional g-C3N4/PDA (CNP) nanocarrier platform was prepared. The π-conjugation system in PDA and the electronegative hydroxyl groups on the surface of CNP promote the creation of abundant active sites, which had a high drug loading rate of about 98.5 % for the electropositive GA. Due to the strong NIR reaction of CNP, the release of GA from CNP/GA can be greatly accelerated by the rising temperature, bonding disruption and charge transfer. Moreover, the photo-generated electron-hole pairs could be excited by the NIR effect of CNP, which promotes the production of ROS (·OH, ·O2– and 1O2) to induce apoptosis in HepG2 cells. Thus, the present spherical CNP nanocarrier with a combination of enzyme-mimic activity and NIR-responsive properties has a great potential for chemo-photothermal synergistic tumor therapy.

Beta cyclodextrin conjugated Au[sbnd]Fe3O4 Janus nanoparticles with enhanced chemo-photothermal therapy performance

The strategic integration of multi-functionalities within a singular nanoplatform has received growing attention for enhancing treatment efficacy, particularly in chemo-photothermal therapy. This study introduces a comprehensive concept of Janus nanoparticles (JNPs) composed of Au and Fe3O4 nanostructures intricately bonded with β-cyclodextrins (β-CD) to encapsulate 5-Fluorouracil (5-FU) and Ibuprofen (IBU). This strategic structure is engineered to exploit the synergistic effects of chemo-photothermal therapy, underscored by their exceptional biocompatibility and photothermal conversion efficiency (∼32.88 %). Furthermore, these β-CD-conjugated JNPs enhance photodynamic therapy by generating singlet oxygen (1O2) species, offering a multi-modality approach to cancer eradication. Computer simulation results were in good agreement with in vitro and in vivo assays. Through these studies, we were able to prove the improved tumor ablation ability of the drug-loaded β-CD-conjugated JNPs, without inducing adverse effects in tumor-bearing nude mice. The findings underscore a formidable tumor ablation potency of β-CD-conjugated Au-Fe3O4 JNPs, heralding a new era in achieving nuanced, highly effective, and side-effect-free cancer treatment modalities. Statement of significanceThe emergence of multifunctional nanoparticles marks a pivotal stride in cancer therapy research. This investigation unveils Janus nanoparticles (JNPs) amalgamating gold (Au), iron oxide (Fe3O4), and β-cyclodextrins (β-CD), encapsulating 5-Fluorouracil (5-FU) and Ibuprofen (IBU) for synergistic chemo-photothermal therapy. Demonstrating both biocompatibility and potent photothermal properties (∼32.88 %), these JNPs present a promising avenue for cancer treatment. Noteworthy is their heightened photodynamic efficiency and remarkable tumor ablation capabilities observed in vitro and in vivo, devoid of adverse effects. Furthermore, computational simulations validate their interactions with cancer cells, bolstering their utility as an emerging therapeutic modality. This endeavor pioneers a secure and efficacious strategy for cancer therapy, underscoring the significance of β-CD-conjugated Au-Fe3O4 JNPs as innovative nanoplatforms with profound implications for the advancement of cancer therapy.

Multifunctional iron oxide‐hydroxide based nanorods for hydrogen sulfide scavenging assisted synergistic photothermal-chemotherapy of colon cancer

The tumor microenvironment responsive multifunctional nanoplatforms with integrated diagnosis and therapy have recently received great attention in anti-cancer treatment. In this study, we developed biocompatible iron oxide-hydroxide-based nanorods (DOX-FPT NRs) for MR imaging and H2S scavenging assisted synergistic photothermal-chemotherapy of colon cancer, which is fabricated by modifying polydopamine (PDA) and transferrin (Tf) on the surface of iron oxide hydroxide (FeOOH) nanorods. The prepared DOX-FPT NRs could precisely target the colon cancer cells through transferrin ligand-receptor-mediated targeting and effectively scavenge endogenous H2S to prohibit the growth of colon cancer. Meanwhile, the considerable drug loading capability and outstanding photothermal conversion efficiency are permitted by the PDA shell modification. In addition, the H2S scavenging assisted photothermal-chemotherapy showed an excellent therapeutic effect on CT26 cells via in vitro cell test. Therefore, the prepared DOX-PFT NRs will be a promising nanoplatform to enhance the therapeutic effect of colon cancer through the treatment strategy of H2S scavenging-assisted synergistic photothermal chemotherapy.

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 hyaluronic acid-altered gold complex delivery for head and neck squamous cell carcinoma therapy with high antitumor efficacy and low in vivo toxicity

The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.

Synergistic chemo-photothermal therapy using gold nanorods supported on thiol-functionalized mesoporous silica for lung cancer treatment

Cancer therapy necessitates the development of novel and effective treatment modalities to combat the complexity of this disease. In this project, we propose a synergistic approach by combining chemo-photothermal treatment using gold nanorods (AuNRs) supported on thiol-functionalized mesoporous silica, offering a promising solution for enhanced lung cancer therapy. To begin, mesoporous MCM-41 was synthesized using a surfactant-templated sol–gel method, chosen for its desirable porous structure, excellent biocompatibility, and non-toxic properties. Further, thiol-functionalized MCM-41 was achieved through a simple grafting process, enabling the subsequent synthesis of AuNRs supported on thiol-functionalized MCM-41 (AuNR@S-MCM-41) via a gold-thiol interaction. The nanocomposite was then loaded with the anticancer drug doxorubicin (DOX), resulting in AuNR@S-MCM-41-DOX. Remarkably, the nanocomposite exhibited pH/NIR dual-responsive drug release behaviors, facilitating targeted drug delivery. In addition, it demonstrated exceptional biocompatibility and efficient internalization into A549 lung cancer cells. Notably, the combined photothermal-chemo therapy by AuNR@S-MCM-41-DOX exhibited superior efficacy in killing cancer cells compared to single chemo- or photothermal therapies. This study showcases the potential of the AuNR@S-MCM-41-DOX nanocomposite as a promising candidate for combined chemo-photothermal therapy in lung cancer treatment. The innovative integration of gold nanorods, thiol-functionalized mesoporous silica, and pH/NIR dual-responsive drug release provides a comprehensive and effective therapeutic approach for improved outcomes in lung cancer therapy. Future advancements based on this strategy hold promise for addressing the challenges posed by cancer and transforming patient care.

Dual-functional nano-carrier system based on NIR-laser-triggered dynamic Au[sbnd]Se interaction for chemo-photothermal synergistic tumor therapy

Photothermal therapy (PTT) combined with chemotherapy has been highly desirable to improve the tumor treatment efficacy. Here, we report a novel controlled release nano-carrier system named Se-PEG-Au NPs-DOX (SePAD) for achieving chemo-photothermal synergistic tumor therapy. In this system, the diselenide-containing co-polymers (mPEG-Se–Se-PEGm) were anchored onto the surface of Au NPs via AuSe interactions and the soluble chemotherapeutic doxorubicin (Dox) was loaded into the monolayers. This structure is proved to be stable in a high biological thiols environment. Strikingly, the SePAD presents an ideal efficient photothermal capability and a controllable Dox release behavior by dynamic AuSe interaction in GSH-rich tumor cells when irradiated under 808 nm NIR laser. Following, the results of in vitro and in vivo experiments all demonstrat the superior antitumor properties of SePAD in murine breast cancer. Thus, this system provides a promising strategy to realize chemo-photothermal synergistic combination therapy for breast tumors.

Synergistic Chemo-Photothermal Therapy of Breast Cancer Based on Mesoporous Polydopamine Nanoparticles Decorated with Atovaquone

Synergistic Chemo-Photothermal Therapy of Breast Cancer Based on Mesoporous Polydopamine Nanoparticles Decorated with Atovaquone

Supramolecular self-assembled gold nanoparticle clusters for synergistic photothermal-chemo tumor therapy.

The combination of photothermal therapy and chemotherapy has emerged as a promising strategy to improve cancer therapeutic efficacy. However, developing a versatile nanoplatform that simultaneously possesses commendable photothermal effect and high drug encapsulation efficiency remains a challenging problem yet to be addressed. Herein, we report a facile supramolecular self-assembly strategy to construct gold nanoparticle clusters (AuNCs) for synergistic photothermal-chemo therapy. By utilizing the functional polysaccharide as a targeted ligand, hyaluronic acid-enriched AuNCs were endowed with targeting CD44 receptor overexpressed on the B16 cancer cells. Importantly, these hyaluronic acid modified AuNCs can shelter therapeutic cargo of doxorubicin (DOX) to aggregate larger nanoparticles via a host-guest interaction with the anchored β-cyclodextrin, as a "nanocluster-bomb" (DOX@AuNCs). The in vitro results revealed that these DOX@AuNCs showed light-triggered drug release behavior and synergistic photothermal-chemo therapy. The improved efficacy of synergistic therapy was further demonstrated by treating a xenografted B16 tumor model in vivo. We envision that our multipronged design of DOX@AuNCs provides a potent theranostic platform for precise cancer therapy and could be further enriched by introducing different imaging probes and therapeutic drugs as appropriate suitable guest molecules.

Multi-Stimuli-Responsive and Cell Membrane Camouflaged Aggregation-Induced Emission Nanogels for Precise Chemo-photothermal Synergistic Therapy of Tumors.

Targeted and controllable drug release at lesion sites with the aid of visual navigation in real-time is of great significance for precise theranostics of cancers. Benefiting from the marvelous features (e.g., bright emission and phototheranostic effects in aggregates) of aggregation-induced emission (AIE) materials, constructing AIE-based multifunctional nanocarriers that act as all-arounders to integrate multimodalities for precise theranostics is highly desirable. Here, an intelligent nanoplatform (P-TN-Dox@CM) with homologous targeting, controllable drug release, and in vivo dual-modal imaging for precise chemo-photothermal synergistic therapy is proposed. AIE photothermic agent (TN) and anticancer drug (Dox) are encapsulated in thermo-/pH-responsive nanogels (PNA), and the tumor cell membranes are camouflaged onto the surface of nanogels. Active targeting can be realized through homologous effects derived from source tumor cell membranes, which advantageously elevates the specific drug delivery to tumor sites. After being engulfed into tumor cells, the nanogels exhibit a burst drug release at low pH. The near-infrared (NIR) photoinduced local hyperthermia can activate severe cytotoxicity and further accelerate drug release, thus generating enhanced synergistic chemo-photothermal therapy to thoroughly eradicate tumors. Moreover, P-TN-Dox@CM nanogels could achieve NIR-fluorescence/photothermal dual-modal imaging to monitor the dynamic distribution of therapeutics in real-time. This work highlights the great potential of smart P-TN-Dox@CM nanogels as a versatile nanoplatform to integrate multimodalities for precise chemo-photothermal synergistic therapy in combating cancers.

PH/glutathione dual-responsive copper sulfide-coated organic mesoporous silica for synergistic chemo-photothermal therapy

Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials.

Nano-injectable pH/NIR-responsive hydrogel for chemo-photothermal synergistic drug delivery.

Conventional cancer treatments are highly toxic and ineffective; therefore, it is essential to develop less toxic and minimally invasive treatment methods. A pH/Near Infra-red (NIR) dual-responsive, nano-injectable smart hydrogel was fabricated by incorporating CuS nanoparticles into the hydrogel networks formed by a random copolymer of N-isopropylacrylamide (NIPAM) and double-bond functionalized uracil. Microstructural characterizations of synthesized polymer and hydrogels were carried out using transmission electron microscope (TEM), scanning electron microscope (SEM), nuclear magnetic resonance (NMR) and fourier transform infrared spectroscopy (FT-IR). Multiple hydrogen bonding interactions between uracils function as physical cross-linking points to construct the network structure of the polymeric nanogel without the addition of additional cross-linking agents, ensuring the material's safety. The amino group on the structure of uracil gives the uracil-modified polymeric hydrogel excellent pH responsiveness. Notably, as a temperature-responsive material, poly (N-isopropylacrylamide) (PNIPAM) nanogel solution can achieve in situ gel formation (within 100 s at 37°C) above its lower critical solution temperature (LCST), granting injectability to polymeric solutions. Moreover, using a hierarchical construction strategy, the variable loading of DOX and CuS was achieved. First, a heterogeneous system was created by encapsulating doxorubicin (DOX) inside the nanogel via hydrophobic and π-π stacking interactions, followed by the introduction of CuS nanoparticles as photosensitizers outside of the nanogels. Due to the presence of CuS nanoparticles, the gel is able to convert NIR light into local heat to enhance the destruction of tumor cells while simultaneously achieving rapid in situ gel formation. The in situ-forming hydrogel showed promising tissue biocompatibility. The in vitro antitumor test demonstrated the capacity of the nanocomposite hydrogel for chemo-photothermal synergistic therapy. Therefore, this prepared platform has the potential to become a safe and effective, smart-responsive drug carrier for chemotherapy and PTT synergy, a minimally invasive material for tumor treatment.

Polypyrrole nanoparticles loaded with doxorubicin for pH-responsive combinational photothermal-chemotherapy of cancer cells

The combined treatment method integrated photothermal therapy (PTT) with chemotherapy is extremely promising owing to the synergistic therapeutic effect as compared to single PTT or chemotherapy. To facilitate more novel and facile photothermal-chemotherapy drugs as well as promote controllable combination therapy, we have developed a mild and facile method to fabricate polymer polypyrrole (PPy)-doxorubicin (DOX) nanoparticles (NPs) as pH-responsive drug nanocarriers for synergistic photothermal-chemotherapy. In the nanoplatform, poly-L-lysine (PLL)-modified PPy serves as the photothermal material, and (DOX) molecules are adopted as the chemotherapy agent. Based on the cross-linking reaction of glutaraldehyde, DOX molecules are flexibly and efficiently assembled on the surface of PLL-modified PPy NPs. The obtained PPy-DOX NPs possess high photothermal effect, superior loading capacity of DOX, and controlled drug release behavior. The combination photothermal-chemotherapy based on PPy-DOX NPs has significantly enhanced the antitumor therapy effect. In general, the designed PPy-DOX NPs may be a potential drug delivery nanoplatform for cancer combination therapy.

B7H3 targeting gold nanocage pH-sensitive conjugates for precise and synergistic chemo-photothermal therapy against NSCLC

BackgroundThe combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC).ResultsIn vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts.ConclusionThis study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.

HER2-targeting two-dimensional black phosphorus as a nanoplatform for chemo-photothermal therapy in breast cancer

Trastuzumab (Tmab) targeted therapy or its combination with chemotherapy is normally insufficient to elicit a comprehensive therapeutic response owing to the inherent or acquired drug resistance and systemic toxicity observed in highly invasive HER2-positive breast cancer. In this study, we propose a novel approach that integrates photothermal therapy (PTT) with targeted therapy and chemotherapy, thereby achieving additive or synergistic therapeutic outcomes. We utilize PEGylated two-dimensional black phosphorus (2D BP) as a nanoplatform and photothermal agent to load chemotherapeutic drug mitoxantrone (MTO) and conjugate with Tmab (BP-PEG-MTO-Tmab). The in vitro and in vivo experiments demonstrated that the HER2-targeting BP-PEG-MTO-Tmab complexes exhibited desirable biocompatibility, safety and enhanced cancer cell uptake efficiency, resulting in increased accumulation and prolonged retention of BP and MTO within tumors. Consequently, the complex improved photothermal and chemotherapy treatment efficacy in HER2-positive cells in vitro and a subcutaneous tumor model in vivo, while minimized harm to normal cells and showed desirable organ compatibility. Collectively, our study provides compelling evidence for the remarkable efficacy of targeted and synergistic chemo-photothermal therapy utilizing all-in-one nanoparticles as a delivery system for BP and chemotherapeutic drug in HER2-positive breast cancer.

A Versatile PDA(DOX) Nanoplatform for Chemo-Photothermal Synergistic Therapy against Breast Cancer and Attenuated Doxorubicin-Induced Cardiotoxicity

Photothermal therapy (PTT) is a highly clinical application promising cancer treatment strategy with safe, convenient surgical procedures and excellent therapeutic efficacy on superficial tumors. However, a single PTT is difficult to eliminate tumor cells completely, and tumor recurrence and metastasis are prone to occur in the later stage. Chemo-photothermal synergistic therapy can conquer the shortcomings by further killing residual tumor cells after PTT through systemic chemotherapy. Nevertheless, chemotherapy drugs' extreme toxicity is also a problematic issue to be solved, such as anthracycline-induced cardiotoxicity. Herein, we selected polydopamine nanoparticles (PDA) as the carrier of the chemotherapeutic drug doxorubicin (DOX) to construct a versatile PDA(DOX) nanoplatform for chemo-photothermal synergistic therapy against breast cancer and simultaneously attenuated DOX-induced cardiotoxicity (DIC). The excellent photothermal properties of PDA were used to achieve the thermal ablation of tumors. DOX carried out chemotherapy to kill residual and occult distant tumors. Furthermore, the PDA(DOX) nanoparticles significantly alleviate DIC, which benefits from PDA's excellent antioxidant enzyme activity. The experimental data of the chemotherapy groups showed that the results of the PDA(DOX) group were much better than the DOX group. This study not only effectively inhibits cancer but tactfully attenuates DIC, bringing a new perspective into synergistic therapy against breast cancer.Graphical

Folate-receptor-targeted co-self-assembly carrier-free gemcitabine nanoparticles loading indocyanine green for chemo-photothermal therapy.

The carrier-free chemo-photothermal therapy has become a promising strategy to improve anti-cancer therapeutic efficacy owing to the combination of chemotherapy and photothermal therapy, with improved chemotherapy drug pharmacodynamics and pharmacokinetics, high drug loading, and reduced toxicity. We designed a novel carrier-free targeting nanoparticles, co-self-assembled amphiphilic prodrugs 3',5'-dioleoyl gemcitabine (DOG), and tumor-targeted γ-octadecyl folate (MOFA), with encapsulated US Food and Drug Administration (FDA)-approved photosensitizer indocyanine green (ICG) for synergistic chemo-photothermal therapy. The DOG linking oleic acid to the sugar moiety of gemcitabine (GEM) showed better self-assembly ability among GEM amphiphilic prodrugs linking different fatty acids. The readily available and highly reproducible 3',5'-dioleoyl gemcitabine/γ-octadecyl folate/indocyanine green (DOG/MOFA/ICG) nanoparticles were prepared by reprecipitation and showed nano-scale structure with mono-dispersity, great encapsulation efficiency of ICG (approximately 74%), acid- and laser irradiation-triggered GEM release in vitro and sustained GEM release in vivo after intravenous administration as well as excellent temperature conversion (57.0°C) with near-infrared laser irradiation. The combinational DOG/MOFA/ICG nanoparticles with near-infrared laser irradiation showed better anti-tumor efficacy than individual chemotherapy or photothermal therapy, with very low hemolysis and inappreciable toxicity for L929 cells. This co-self-assembly of the ICG and the chemotherapy drug (GEM) provides a novel tactic for the rational design of multifunctional nanosystems for targeting drug delivery and theranostics.