Metal-Organic Framework/Graphene Quantum Dot Nanoparticles Used for Synergistic Chemo- and Photothermal Therapy.
ABSTRACT: In this study, a simple one-pot method was used to prepare a multifunctional platform for synergistic chemo- and photothermal therapy,, which is composed of zeolitic imidazolate framework-8 (ZIF-8) as drug nanocarriers and the embedded graphene quantum dots (GQDs) as local photothermal seeds. The structure, drug release behavior, photothermal effect, and synergistic therapeutic efficiency of the ZIF-8/GQD nanoparticles were systematically investigated. Using doxorubicin (DOX) as a model anticancer drug, the results showed that monodisperse ZIF-8/GQD nanoparticles with a particle size of 50-100 nm could encapsulate DOX during the synthesis procedure and trigger DOX release under acidic conditions. The DOX-loaded ZIF-8/GQD nanoparticles could efficiently convert near-infrared (NIR) irradiation into heat and thereby increase the temperature. More importantly, with breast cancer 4T1 cells as a model cellular system, the results indicated that the combined chemo- and photothermal therapy with DOX-ZIF-8/GQD nanoparticles exhibited a significant synergistic effect, resulting in a higher efficacy to kill cancer cells compared with chemotherapy and photothermal therapy alone. Hence, ZIF-8/GQD nanoparticles would be promising as versatile nanocarriers for synergistic cancer therapy.
Project description:Background:Carbon-based drug delivery systems have attracted great interest because of their excellent photothermal conversion capability and high specific surface area for drug loading. Herein, we report a multifunctional nanoplatform based on hyaluronic acid (HA)-modified and graphene quantum dot (GQD)-gated hollow mesoporous carbon nanoparticle (HMCN) for anticancer drug encapsulation and targeted chemo-photothermal therapy of CD44 receptor-overexpressed cancer cells. Methods:In this design, HMCN was not only used as a nanocarrier with high drug loading content to achieve chemotherapy, but also as a near-infrared absorbing agent to realize photothermal therapy. GQDs could not only prevent premature drug release during blood circulation, but also enhance the chemo-photothermal therapeutic efficacy for complete tumor growth suppression. After being modified with HA, the HA-HMCN(DOX)@GQDs could specifically target cancer cells. Results:As expected, the as-prepared HMCN exhibited high doxorubicin (DOX)-loading capacity of 410 mg/g and excellent light-to-heat conversion property. The DOX was released from HA-HMCN(DOX)@GQDs in a near-infrared laser and pH stimuli-responsive manner, which could enhance the therapeutic effect. In vitro cell biological experimental results confirmed that the nanoplatform possesses excellent biocompatibility, specifically target CD44 receptor-overexpressing human cervical carcinoma HeLa cells, and has remarkable synergistic chemo-photothermal killing capacity. The in vivo therapeutic studies in HeLa xenografts also showed negligible toxicity of HA-HMCN@GQDs and complete inhibition of tumor growth of HA-HMCN(DOX) @GQDs with near-infrared irradiation. Conclusion:The excellent therapeutic effects demonstrated in vitro and in vivo suggested the HMCN-based nanoplatform holds potential for efficient dual-responsive targeting drug delivery and synergistic chemo-photothermal therapy.
Project description:For an ideal drug delivery system, the outstanding drug-loading capacity and specific control of the release of therapeutics at the desired lesions are crucial. In this work, we developed a triple-responsive nanoplatform based on copper sulfide (CuS)-capped yolk-shell-structured periodic mesoporous organosilica nanoparticles (YSPMOs) for synergetic chemo-photothermal therapy.Herein, the YSPMOs were employed as a drug carrier, which exhibited a high doxorubicin (DOX) loading capacity of 386 mg/g. In this controlled-release drug delivery system, CuS serves as a gatekeeper to modify YSPMOs with reduction-cleavable disulfide bond (YSPMOs@CuS). CuS could not only avoid premature leakage in the delivery process, but also endowed the excellent photothermal therapy (PTT) ability.Upon entering into cancer cells, the CuS gatekeeper was opened with the breaking of disulfide bonds and the DOX release from YSPMOs(DOX)@CuS in response to the intracellular acidic environment and external laser irradiation. Such a precise control over drug release, combined with the photothermal effect of CuS nanoparticles, is possessed by synergistic chemo-photothermal therapy for cancer treatment. Both in vitro and in vivo experimental data indicated that the synergistic effect of YSPMOs(DOX)@CuS showed efficient antitumor effect. In addition, low systemic toxicity was observed in the pathologic examinations of liver, spleen, lungs, and kidneys.This versatile nanoplatform combination of PTT, chemotherapeutics, and gating components shows general potential for designing multifunctional drug delivery systems.
Project description:Cancer combination therapy to treat tumors with different therapeutic approaches can efficiently improve treatment efficacy and reduce side effects. Herein, we develop a theranostic nano-platform based on polydopamine (PDA) nanoparticles, which then are exploited as a versatile carrier to allow simultaneous loading of indocyanine green (ICG), doxorubicin (DOX) and manganese ions (PDA-ICG-PEG/DOX(Mn)), to enable imaging-guided chemo & photothermal cancer therapy. In this system, ICG acts as a photothermal agent, which shows red-shifted near-infrared (NIR) absorbance and enhanced photostability compared with free ICG. DOX, a model chemotherapy drug, is then loaded onto the surface of PDA-ICG-PEG with high efficiency. With Mn(2+) ions intrinsically chelated, PDA-ICG-PEG/DOX(Mn) is able to offer contrast under T1-weighted magnetic resonance (MR) imaging. In a mouse tumor model, the MR imaging-guided combined chemo- & photothermal therapy achieves a remarkable synergistic therapeutic effect compared with the respective single treatment modality. This work demonstrates that PDA nanoparticles could serve as a versatile molecular loading platform for MR imaging guided combined chemo- & photothermal therapy with minimal side effects, showing great potential for cancer theranostics.
Project description:Multifunctional supramolecular nanoplatforms that integrate the advantages of different therapeutic techniques can trigger multimodal synergistic treatment of tumors, thus representing an emerging powerful tool for cancer therapeutics. Methods: In this work, we design and fabricate a multifunctional supramolecular drug delivery platform, namely Fa-mPEG@CP5-CuS@HMSN-Py nanoparticles (FaPCH NPs), consisting of a pyridinium (Py)-modified hollow mesoporous silica nanoparticles-based drug reservoir (HMSN-Py) with high loading capacity, a layer of NIR-operable carboxylatopillararene (CP5)-functionalized CuS nanoparticles (CP5-CuS) on the surface of HMSN-Py connected through supramolecular host-guest interactions between CP5 rings and Py stalks, and another layer of folic acid (Fa)-conjugated polyethylene glycol (Fa-PEG) antennas by electrostatic interactions capable of active targeting at tumor lesions, in a controlled, highly integrated fashion for synergistic chemo-photothermal therapy. Results: Fa-mPEG antennas endowed the enhanced active targeting effect toward cancer cells, and CP5-CuS served as not only a quadruple-stimuli responsive nanogate for controllable drug release but also a special agent for NIR-guided photothermal therapy. Meanwhile, anticancer drug doxorubicin (DOX) could be released from the HMSN-Py reservoirs under tumor microenvironments for chemotherapy, thus realizing multimodal synergistic therapeutics. Such a supramolecular drug delivery platform showed effective synergistic chemo-photothermal therapy both in vitro and in vivo. Conclusion: This novel supramolecular nanoplatform possesses great potential in controlled drug delivery and tumor cellular internalization for synergistic chemo-photothermal therapy, providing a promising approach for multimodal synergistic cancer treatment.
Project description:Near-infrared (NIR)-absorbing conjugated polymer nanoparticles are interesting for imaging-guided combination therapy, especially for synergistic photothermal therapy and chemotherapy; however, most of them target tumours passively through the enhanced permeability and retention (EPR) effect, leading to low utilization efficiency. To address this problem, we report an active tumour-targeting strategy of tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles as a new class of drug nanocarriers for imaging-guided combination therapy of cancer. Methods: A tumour-homing chimeric polypeptide C-ELP-F3 was genetically engineered, and chemoselectively conjugated to polypyrrole (PPy) nanoparticles via a facile thiol-maleimide coupling reaction to form ELP-F3 conjugated PPy (PPy-ELP-F3) nanoparticles. Doxorubicin (DOX) was physically adsorbed onto PPy-ELP-F3 nanoparticles to yield DOX-loaded PPy-ELP-F3 (DOX/PPy-ELP-F3) nanoparticles. The physicochemical properties of DOX/PPy-ELP-F3 were characterized. The pharmacokinetics of DOX/PPy-ELP-F3 was studied in a mouse model. The photoacoustic imaging and photothermal imaging of tumours were tested in a melanoma-bearing mouse model. The photothermal-chemical combination therapy of tumours was investigated by using melanoma cells in vitro and in a melanoma-bearing mouse model. Results: DOX/PPy-ELP-F3 nanoparticles showed enhanced cytotoxicity to melanoma cells in vitro and improved tumour-targeting efficiency in vivo, as compared with both DOX/PPy-ELP nanoparticles without the tumour-homing function and free DOX. The photothermal effect of DOX/PPy-ELP-F3 nanoparticles could accelerate the release of DOX from PPy-ELP-F3. Under the guidance of photoacoustic and photothermal imaging, the synergy of photothermal and chemical therapy could completely abolish tumours without detectable systemic toxicity. Conclusion: Tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles are promising as a new multifunctional drug delivery platform for highly-efficient imaging guided combination therapy.
Project description:The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy. Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process. The photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) were simultaneously loaded into RHPPE nanoparticles (denoted as SOHNPCe6/DOX). The therapeutic efficacy of SOHNPCe6/DOX against drug-resistant cancer was evaluated in vitro and in vivo. Results: Under 660-nm light irradiation, SOHNPCe6/DOX can produce SO, which not only induces PDT against cancer but also cleaves the thioketal linkers to destroy the nanoparticles. Subsequently, boosted DOX release can be achieved, activating a chemotherapy cascade to synergistically destroy the remaining tumor cells after the initial round of PDT. Furthermore, SOHNPCe6/DOX also efficiently detected the tumor area by photoacoustic/magnetic resonance bimodal imaging. Under the guidance of bimodal imaging, the laser beam was precisely focused on the tumor areas, and subsequently, SOHNPCe6/DOX realized a cascade of amplified synergistic chemo-photodynamic therapeutic effects. High antitumor efficacy was achieved even in a drug-resistant tumor model. Conclusion: The designed SOHNPCe6/DOX with great biocompatibility is promising for use as a co-delivery carrier for combined chemo-photodynamic therapy, providing an alternative avenue to achieve a cascade of amplified synergistic effects of chemo-photodynamic therapy for cancer treatment.
Project description:The consolidation of different therapies into a single nanoplatform has shown great promise for synergistic tumor treatment. In this study, a multifunctional platform by WS2 quantum dots (WQDs)-coated doxorubicin (DOX)-loaded periodic mesoporous organosilicas (PMOs-DOX@WQDs) nanoparticles were fabricated for the first time, and which exhibits good potential for synergistic chemo-photothermal therapy.The structure, light-mediated drug release behavior, photothermal effect, and synergistic therapeutic efficiency of PMOs-DOX@WQDs to HCT-116 colon cancer cells were investigated. The thioether-bridged PMOs exhibit a high DOX loading capacity of 66.7 ?g mg-1. The gating of the PMOs not only improve the drug loading capacity but also introduce the dual-stimuli-responsive performance. Furthermore, the as-synthesized PMOs-DOX@WQDs nanoparticles can efficiently generate heat to the hyperthermia temperature with near infrared laser irradiation.It was confirmed that PMOs-DOX@WQDs exhibit remarkable photothermal effect and light-triggered faster release of DOX. More importantly, it was reasonable to attribute the efficient anti-tumor efficiency of PMOs-DOX@WQDs.The in vitro experimental results confirm that the fabricated nanocarrier exhibits a significant synergistic effect, resulting in a higher efficacy to kill cancer cells. Therefore, the WQD-coated PMOs present promising applications in cancer therapy.
Project description:Chemo-photothermal therapy shows great potential for inhibiting tumor growth. However, achieving maximal chemo-photothermal synergistic efficacy is challenging because of the low efficiency of controllable chemo-drug release in response to external or internal triggers. Thus, a nano-delivery system that could effectively achieve photothermal therapy and dual stimuli-responsive (heat and pH) drug release to inhibit both primary breast tumor growth and metastases is required. Methods: Herein, a thermo- and pH-responsive polymer (mPEG-PAAV) with an upper critical solution temperature (UCST) was synthesized to fabricate a DOX- and IR780-loaded micellar system. After systematic studies of the photothermal performance and controllable drug release of mPEG-PAAV micelles/IR780+DOX under NIR irradiation at different pH values, their chemo-photothermal synergetic therapy efficacies were also estimated both in in vitro and in vivo. Results: Because of the photothermal conversion of mPEG-PAAV micelle/IR780+DOX (~200 nm, 3.82 mV), high local temperature could be induced at the tumor site under NIR laser irradiation. This hyperthermia not only produced an enhanced tumor necrosis, but also broke down the micelles under the decreased pH environment, resulting in rapid DOX release and enhanced intracellular drug accumulation after NIR laser irradiation. In addition, photoacoustic imaging (PAI) of mPEG-PAAV/IR780+DOX micelle was adopted to monitor the morphology and micro-vascular distribution of the tumor tissue, which could also guide the chemo-photothermal therapy. Most importantly, the systemic administration of mPEG-PAAV micelles/IR780+DOX combined with NIR laser irradiation could simultaneously eliminate the 4T1 breast tumor and thoroughly suppress lung metastasis without any obvious adverse effects. Conclusion: Herein, a pH- and thermo-dual responsive UCST micelle system was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and PA imaging guidance for chemo-photothermal synergistic therapy of both primary breast tumors and their metastases.
Project description:The integration of photothermal therapy and chemotherapy has been recognized to be an efficient strategy through the instant thermally ablation and long-term chemical inhibition, thus achieving high therapeutical effect. In the present work, we designed and prepared Cu7S4@SiO2/DOX nanocomposites and used them as efficient nanoplatforms for synergistic photothermal-chemo therapy on melanoma tumors. The Cu7S4@SiO2/DOX was constructed by firstly synthesizing Cu7S4 nanocrystals, then in situ growing SiO2 shell on the surface of Cu7S4 nanocrystals, and finally loading DOX within SiO2 shell. The Cu7S4@SiO2/DOX was composed of Cu7S4 core as the photothermal transducer, SiO2 shell as DOX carrier and DOX as the model of anticancer drug. Once exposed to a 1064 nm laser, the Cu7S4@SiO2/DOX could simultaneous generate heat for photothermal therapy and accelerate the DOX release. When the Cu7S4@SiO2/DOX was injected into the center of tumor, the tumor exhibit rapid temperature elevation once exposed to the NIR laser and the tumor growth is significantly inhibited through the synergistic photothermal-chemo therapy, in comparison to the limited therapeutical effect of photothermal therapy or chemotherapy alone. Therefore, the Cu7S4@SiO2/DOX with photothermal-chemo function can be used as excellent nanoplatforms for treating solid tumor with high theoretical effect.
Project description:The development of biomimetic nanoparticles with functionalities of natural biomaterial remains a major challenge in cancer combination therapy. Herein, we developed a tumor-cell-derived exosome-camouflaged porous silicon nanoparticles (E-MSNs) as a drug delivery system for co-loading ICG and DOX (ID@E-MSNs), achieving the synergistic effects of chemotherapy and photothermal therapy against breast cancer. Compared with ID@MSNs, the biomimetic nanoparticles ID@E-MSNs can be effectively taken up by the tumor cell and enhance tumor accumulation with the help of the exosome membrane. ID@E-MSNs also retain the photothermal effect of ICG and cytotoxicity of DOX. Under 808 nm near infrared irradiation, ICG can produce hyperthermia to collapse E-MSNs nanovehicles, accelerate drug release, and induce tumor ablation, achieving effective chemo-photothermal therapy. In vivo results of 4T1 tumor-bearing BALB/c mice showed that ID@E-MSNs could accumulate tumor tissue and inhibit the growth and metastasis of tumor. Thus, tumor exosome-biomimetic nanoparticles indicate a proof-of-concept as a promising drug delivery system for efficient cancer combination therapy.