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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Redox-sensitive micelles assembled from amphiphilic mPEG-PCL-SS-DTX conjugates for the delivery of docetaxel

Huiyuan Zhang,Kaiming Wang,Pei Zhang,Wenxiu He,Aixin Song,Yuxia Luan

Docetaxel (DTX) can produce anti-tumor effects by inhibiting cell growth and inducing apoptosis. However, the poor solubility of DTX restricts its application and its clinical formulation has caused serious adverse reaction due to the use of Tween-80. In the present study, DTX was conjugated to an amphiphilic di-block polymer to solve these problems. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was selected as the polymer skeleton and a redox sensitive disulfide bond was used as the linker between DTX and mPEG-PCL. The synthesized mPEG-PCL-SS-DTX conjugates were characterized by 1 H-nuclear magnetic resonance ( 1 H NMR) and Fourier transform infrared spectroscopy (FTIR). Interestingly, the mPEG-PCL-SS-DTX conjugates could self-assemble into micelles in aqueous solution. The critical micelle concentration (CMC) of mPEG-PCL-SS-DTX micelles was about 2.3   mg   L −1 determined using pyrene molecule fluorescent probe method while the size of mPEG-PCL-SS-DTX micelles was determined to be ca . 17.6   nm and 116.0   nm with a bimodal distribution by dynamic light scattering (DLS). The in vitro release results indicated that the as-prepared micelles exhibited a sustained release profile with good redox sensitive properties. In particular, the hemolytic toxicity test indicated the as-prepared mPEG-PCL-SS-DTX micelles had negligible hemolytic activity, demonstrating their safety in drug delivery system. Cytotoxicity assay of the mPEG-PCL-SS-DTX micelles verified their highly enhanced cytotoxicity to MCF-7/A and A549 cells. These results thus demonstrated that the present redox-sensitive mPEG-PCL-SS-DTX micelle was an efficient and safe sustained drug delivery system in the biomedical area.

研究领域: 药剂学 · 肿瘤学 · 生物医学工程
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FOOD CHEMISTRY · 2023 · IF 8.8

Bacterial cellulose loaded with silver nanoparticles as a flexible, stable and sensitive SERS-active substrate for detection of the shellfish toxin DTX-1

Ruiyun You,Haonan Wang,Chuyi Wang,Jiali Huang,Huina Zhu,Yunzhen Liu,Jian-Han Zhang,Jiewen Liu,Xiaowei Yu,Yudong Lu

Diarrheal shellfish toxins are considered one of the most lethal red tide algae toxins in the worldwide. In this work, we propose an Ag NPs-loaded bacterial cellulose membrane (BCM) surface-enhanced Raman scattering (SERS) sensor based on an aptamer (Apt) for the ultrasensitive detection of dinophysistoxin (DTX-1), a type of diarrheal shellfish toxin. During drying, Ag NPs can be further densified on “gel-like” BCM to form high-density SERS “hot spots”. We developed the “Apt-SH@Ag NPs@BCM” SERS sensor and used the competition of DTX-1 and complementary base (Cob) in the process of base complementary pairing to achieve SERS detection of DTX-1, with a minimum detection limit of 9.5 × 10 −10  mol/L. Sample assays showed DTX-1 recovery rates ranging from 95.8% and 108.2% and the detection results were comparable to those obtained by LC–MS. Therefore, this work holds great potential for detecting of toxic substances in shellfish products, especially for the oyster (portuguese oyster) and mussel (blue mussel).

研究领域: 食品科学 · 分析化学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

TUBB3/DTX LNPs Dry Powder Inhaler and an Efficient Delivery Device for Targeted Therapy of Lung Cancer

Mingyuan Li,Xianglong Wang,Mengsi Yin,Faxin Zhang,Wenlin Ma,Linze Che,Jinhao Yu,Yan Cheng,Mengju Xu,Xiaofu Liang,Wen Su,Hongmeng Ren,Weixue Si,Jingsi Ma,Shaodan Peng,Xiaolong Zhao,Jiaping Zhou,Ziqi Wu,Jiang Deng,Hua Sun

Lung cancer is the most prevalent and deadly tumor globally, marked by drug resistance and a poor prognosis. Specialized formulations with strong lung targeting are currently lacking. Docetaxel (DTX) and TUBB3-siRNA represent chemotherapy and RNA interference (RNAi), two strategies for lung cancer treatment. Lipid nanoparticles (LNPs) are nanocarriers suitable for nucleic acid delivery. In this study, spray freeze-drying (SFD) converted LNP colloidal solutions into inhalable dry powders. Fresh and rehydrated LNP (SFD) showed sizes below 200 nm, ζ potentials near 0 mV, and uniform roundness by transmission electron microscopy. The geometric particle size distribution (D50) of TUBB3-LNPs, DTX-LNPs, and TUBB3/DTX-LNPs inhalable powders did not differ significantly (1.99–5.90 μm). The median mass aerodynamic diameter (MMAD) was 2.61 ± 0.32 μm, suitable for pulmonary deposition. Experiments with BEAS-2B and H460 cells showed that TUBB3/DTX-LNPs had low cytotoxicity and good biocompatibility with BEAS-2B but strongly inhibited H460 cells. Differences in apoptosis induced by fresh LNPs and rehydrated LNP (SFD) indicate that the SFD process preserves normal cell viability while maintaining tumor inhibition. Because dry powder inhalers combine the drug formulation with the delivery device, a specialized single-dose prefilled device was developed that featured four symmetrically configured orifices (vents) located in the middle of the tube body; it achieved a high dry powder emptying rate of 95–100%. Furthermore, this study demonstrated the lung-targeting efficacy and sustained-release properties of the formulation.

CAS / MDL: 38215-36-0
研究领域: 药剂学 · 纳米技术 · 肿瘤学 · 药物递送 · 呼吸医学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Pharmaceutica Sinica B · 2018 · IF 6.014

Efficient lung cancer-targeted drug delivery via a nanoparticle/MSC system

Xusheng Wang,Haiyan Chen,Xiaowei Zeng,Wenpeng Guo,Yu Jin,Shan Wang,Ruiyun Tian,Yanjiang Han,Ling Guo,Jimin Han,Yaojiong Wu,Lin Mei

Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. MSC showed a higher drug intake capacity than fibroblasts. In addition, MSC showed predominant lung trapping in both rabbit and monkey. IR-780 dye, a fluorescent probe used to represent docetaxel (DTX) in NP, delivered via MSC accumulated in the lung. Both in vitro MSC/A549 cell experiments and in vivo MSC/lung cancer experiments validated the intercellular transportation of NP between MSC and cancer cells. In vivo assays showed that the MSC/NP/DTX drug delivery system exerted primary tumor inhibition efficiency similar to that of a NP/DTX drug system. Collectively, the MSC/NP drug delivery system is promising for lung-targeted drug delivery for the treatment of lung cancer and other lung-related diseases.

研究领域: 药理学 · 肿瘤学 · 干细胞研究 · 纳米技术
✓ 已验证 DOI PubMed 高影响因子
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Biomaterials Science · 2018 ·Vol. 6 ·期 5 ·1201-1216 · IF 5.831

α-Lipoic acid stabilized DTX/IR780 micelles for photoacoustic/fluorescence imaging guided photothermal therapy/chemotherapy of breast cancer

WenTing Li,JinRong Peng,Qian Yang,LiJuan Chen,Lan Zhang,XiaoXin Chen,ZhiYong Qian

Micellar nanoparticles have unique advantages as carriers for therapeutic or imaging agents, owing to their smaller size and better penetration of tumors. However, some agents, due to their physical or chemical properties, are difficult to load into micelles. IR780 is one of these agents, and is also a promising near-infrared dye for fluorescence imaging (FI)/photoacoustic imaging (PAI) and cancer photothermal therapy (PTT). Its hydrophobic and high crystallization structure results in limited bioavailability in vivo. It is difficult to load into micelles constructed from an amphiphilic block polymer with relatively low molecular weight. In this study, we use computer simulation and introduce another small biomolecule, α-lipoic acid, into the micelles constructed from a mPEG-PCL copolymer, to lower the energy of molecular interaction between MPEG-PCL and IR780, and expect to enhance the loading capacity of the micelles to IR780. The introduction of α-lipoic acid decreases the energy of molecular interaction between MEPG-PCL and IR780 from −46.18 kJ mol−1 to −196.52 kJ mol−1 and increases the loading capacity and stability of the mPEG-PCL micelles to IR780, which also maintains the loading capacity to DTX. We further construct DTX/IR780 co-loaded mPEG-PCL micelles for FI/PAI dual modal imaging guided PTT/chemotherapy of cancer. By FI and PAI evaluation in vitro and in vivo, we demonstrate that the DTX/IR780 co-loaded micelles can be used as FI and PAI probes. By further evaluating the therapeutic outcome of PTT/chemotherapy co-therapy of breast cancer, we demonstrate that the DTX/IR780 co-loaded mPEG-PCL micelles can serve as promising candidates for FI and PAI guided PTT/chemotherapy of breast cancer.

CAS / MDL: 64-17-5
研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 药学 · 医学成像
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2017 · IF 3.887

Reduction-sensitive mixed micelles assembled from amphiphilic prodrugs for self-codelivery of DOX and DTX with synergistic cancer therapy

Jilian Wu,Huiyuan Zhang,Xu Hu,Ruiling Liu,Wei Jiang,Zhonghao Li,Yuxia Luan

Clinically, codelivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. In this work, we developed a new reduction-sensitive mixed micellar system for self-codelivery of doxorubicin (DOX) and docetaxel (DTX). Biodegradable methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was coupled with DOX and DTX by a reduction-sensitive disulfide bond, resulting in mPEG-PCL-SS-DOX and mPEG-PCL-SS-DTX, respectively. mPEG-PCL-SS-DOX was mixed with mPEG-PCL-SS-DTX at a mole ratio of 1:1 in water, forming a mixed micellar system. The mixed micelles had a diameter of 223.7   nm and a low critical micelle concentration. Reductive-triggered drug release revealed a “smart” characteristic of the mixed micelles. A cellular uptake and cytotoxicity assay in vitro showed that the mixed micelles could efficiently accumulate in MCF-7 cells and suppress the growth of tumour cells. The proposed reduction-sensitive mixed micelles assembled from amphiphilic prodrugs can be used as a promising drug codelivery system for cancer therapy.

研究领域: 药剂学 · 肿瘤学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2023 ·Vol. 28 ·期 16 ·6134 · IF 4.6

cRGD-Conjugated GdIO Nanoclusters for the Theranostics of Pancreatic Cancer through the Combination of T1–T2 Dual-Modal MRI and DTX Delivery

Shengchao Wang,Guiqiang Qi,Zhichen Zhang,Qiangqiang Yin,Na Li,Zhongtao Li,Guangyue Shi,Haifeng Hu,Liguo Hao

Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1–T2dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvβ3on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.Keywords:T1–T2;DTX;MRI;drug delivery;pancreatic cancer

研究领域: 医学影像学 · 纳米技术 · 肿瘤学 · 药物递送系统
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF NANOBIOTECHNOLOGY · 2021 ·Vol. 19 ·期 1 ·1-23 · IF 10.435

A molybdenum oxide-based degradable nanosheet for combined chemo-photothermal therapy to improve tumor immunosuppression and suppress distant tumors and lung metastases

Qiu Na,Yang Xiaoye,Zhang Yanan,Zhang Jicheng,Ji Jianbo,Zhang Yu,Kong Xinru,Xi Yanwei,Liu Dongzhu,Ye Lei,Zhai Guangxi

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.Graphical Abstract

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 免疫学
✓ 已验证 DOI PubMed 高影响因子
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ChemPlusChem · 2016 ·Vol. 81 ·期 11 ·1237-1244 · IF 2.836

Multifunctional Mixed Micelles for Efficient Docetaxol Delivery for Cancer Therapy

Pei Zhang,Wenxiu He,Huiyuan Zhang,Chunzhi Huang,Dujuan Zhao,Yuxia Luan

Graphical Critical micelles concentrate on cancer : Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells. The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ-benzyl l -glutamate)-disulfide-docetaxel (PEG–PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG-SS-DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL −1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl -dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG–PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG–PBLG-SS-DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.

CAS / MDL: 3483-12-3 298-93-1
研究领域: 药学 · 癌症研究 · 纳米技术 · 药物递送系统
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JOURNAL OF NANOBIOTECHNOLOGY · 2021 ·Vol. 19 ·期 1 ·1-24 · IF 10.435

Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery

Hao Wenyan,Cui Yuexin,Fan Yueyue,Chen Mengyu,Yang Guobao,Wang Yuli,Yang Meiyan,Li Zhiping,Gong Wei,Yang Yang,Gao Chunsheng

Background Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m). Results Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n. Conclusion DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy. Graphical Abstract

研究领域: 肿瘤学 · 药学 · 免疫疗法 · 纳米技术
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2022 · IF 9.965

Smart dual responsive nanocarriers with reactive oxygen species amplification assisted synergistic chemotherapy against prostate cancer

Yupeng Guan,Chengyuan Xing,Tongyu Tong,Xinyi Zhang,Jun Li,Huikun Chen,Junfeng Zhu,Yang Kang,Jun Pang

Conventional chemotherapy efficacy is impeded by poor water solubility, inferior tissue targeting, and severe systemic toxic effect. Synergistic chemotherapy has become prominent with the stimulus–response drug delivery system (DDS) to treat solid malignancies. The most popularly employed responsive stimulus is reactive oxygen species (ROS), which is proven to primarily sensitize chemotherapy and enhance antitumor impact. In this study, we have successfully developed smart dual responsive nanocarriers with ROS self-amplification, particularly responding to disassemble under the high levels of ROS and esterase in the tumor microenvironment (TME) and to release docetaxel (DTX) efficiently. Additionally, we utilized palmitoyl ascorbate (PA) as a stabilizer by taking advantage of its amphiphilic structure. PA is also an excellent ROS generator that produces a large amount of hydrogen peroxide (H 2 O 2 ) in TME to achieve ROS self-amplification. Also, elevated levels of ROS could continue to activate ROS-sensitive thioketal and make the remaining nanocarriers disassemble for sustaining the release of chemotherapeutics, realizing a positive feedback loop for ROS generation and ROS amplification, as well as sensitizing chemotherapy efficacy. The smart dual responsive nanocarriers may serve as a promising and prospective strategy for treating prostate cancer and promoting synergistic cancer therapy.

研究领域: 纳米技术 · 癌症治疗 · 药学科学 · 生物医学工程
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Biomaterials Science · 2021 ·Vol. 9 ·期 11 ·3989-4004 · IF 6.843

Oxygen-carrying nanoparticle-based chemo-sonodynamic therapy for tumor suppression and autoimmunity activation

Yanan Zhang,Na Qiu,Yu Zhang,Huixian Yan,Jianbo Ji,Yanwei Xi,Xiaoye Yang,Xiaogang Zhao,Guangxi Zhai

Sonodynamic therapy (SDT) is a promising non-invasive approach for cancer therapy. However, tumor hypoxia, a pathological characteristic of most solid tumor types, poses a major challenge in the application of SDT. In this study, a novel CD44 receptor-targeted and redox/ultrasound-responsive oxygen-carrying nanoplatform was constructed using chondroitin sulfate (CS), reactive oxygen species (ROS)-generating sonosensitizer Rhein (Rh), and perfluorocarbon (PFC). Perfluoroalkyl groups introduced into the structures preserved the oxygen carrying ability of PFC, increasing the oxygen content in B16F10 melanoma cells and enhancing the efficiency of SDT. Controlled nanoparticles without PFC generated lower ROS levels and exerted inferior tumor inhibition effects, both in vitro and in vivo, under ultrasound-treatment. In addition, SDT promoted immunogenic cell death (ICD) by inducing exposure of calreticulin (CRT) after treatment with CS–Rh–PFC nanoparticles (NPs). The immune system was significantly activated by docetaxel (DTX)-loaded NPs after SDT treatment due to the enhanced secretion of IFN-γ, TNF-α, IL-2 and IL-6 cytokines and tumor-infiltrating CD4+ and CD8+ T cell contents. Our findings support the utility of CS–Rh–PFC as an effective anti-tumor nanoplatform that promotes general immunity and accommodates multiple hydrophobic drugs to enhance the beneficial effects of chemo-SDT therapy.

研究领域: 癌症治疗 · 纳米技术 · 免疫学 · 药学
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