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An "all-in-one" antitumor and anti-recurrence/metastasis nanomedicine with multi-drug co-loading and burst drug release for multi-modality therapy.

ABSTRACT: Drug-loading often suffers from tedious procedures, limited loading efficiency, slow release, and therefore a low curative effect. Cancer easily recurs and metastasizes even after a solid tumor is removed. Herein, we report a simple strategy with multi-drug co-loading and burst drug release for a high curative effect and anti-recurrence/metastasis. CuS nanoparticles, protoporphyrin IX, and doxorubicin were added to the precursors of ZIF-8 with one-pot co-loading during the formation of ZIF-8 for chemo-, photothermal-, and photodynamic-therapy to eliminate solid tumors. Negative CpG, as a kind of immune adjuvant, was adsorbed on the positive surface of ZIF-8 to inhibit the recurrence and metastasis of tumors with its long-term immune response. Precision treatment with one-pot multi-drug co-loading, controllable drug delivery, and multi-modality therapy may be anticipated by this versatile strategy.

SUBMITTER: Yang JC

PROVIDER: S-EPMC6148201 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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An "all-in-one" antitumor and anti-recurrence/metastasis nanomedicine with multi-drug co-loading and burst drug release for multi-modality therapy.

Yang Ji-Chun JC Shang Yue Y Li Yu-Hao YH Cui Yu Y Yin Xue-Bo XB

Chemical science 20180730 36

Drug-loading often suffers from tedious procedures, limited loading efficiency, slow release, and therefore a low curative effect. Cancer easily recurs and metastasizes even after a solid tumor is removed. Herein, we report a simple strategy with multi-drug co-loading and burst drug release for a high curative effect and anti-recurrence/metastasis. CuS nanoparticles, protoporphyrin IX, and doxorubicin were added to the precursors of ZIF-8 with one-pot co-loading during the formation of ZIF-8 for ...[more]

PMID: 30288240

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Project description:Rationale: Prostate cancer has become one of the most threatening malignant tumors in men, leading to an imperative need to develop effective and safe therapies. Because of the unique metabolism of tumor cells, the tumor microenvironment (TME) exhibits distinctive properties compared with normal tissues, among which the pH difference has been utilized as an ideal antitumor strategy. Herein, we introduce a reactive oxygen species (ROS)-controlled-release nanosystem with TME-responsiveness by applying hollow mesoporous silica nanoparticles (HMSNs) as carriers loaded with calcium peroxide (CaO2) and coated with polyacrylic acid (PAA) to construct the functional material CaO2@HMSNs-PAA. The differences in pH values and exogenous ROS scavenging abilities between the tumor tissue and normal tissues and the dual pH-responsiveness from CaO2 and PAA lay a scientific foundation for the application of CaO2@HMSNs-PAA in the tumor-selective therapy for prostate cancer. Methods: The morphology and the structure of the nanosystem were characterized by the transmission electron microscope, scanning electron microscope, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, zeta potential, dynamic light scattering measurement, low-angle X-ray diffraction patterns and nitrogen adsorption/desorption isotherm. The CaO2 loading capacity and release profiles in different buffer solutions were determined by inductively coupled plasma-mass spectrometry. The in vitro intracellular uptake of CaO2@HMSNs-PAA was explored on the PC-3 prostate cancer cell line via confocal laser scanning microscopy. The CCK-8 cell proliferation assay was conducted to evaluate the cytotoxicity of CaO2@HMSNs-PAA against PC-3 cells. ROS produced by CaO2@HMSNs-PAA was observed by a fluorescence microscope. The flow cytometry was utilized to analyze the apoptosis of PC-3 cells induced by CaO2@HMSNs-PAA. The Western blot analysis was performed to detect expressions of critical mitochondria-mediated apoptosis markers in PC-3 cells after incubation with CaO2@HMSNs-PAA. The in vivo biosafety and antitumor efficacy were evaluated out on BALB/c mice and BALB/c nude mice subcutaneously transplanted with PC-3 cells, respectively. Results: Comprehensive characterizations indicated the successful synthesis of CaO2@HMSNs-PAA with significant TME-responsiveness. The experimental results demonstrated that the well-developed nanocarrier could efficiently deliver CaO2 to the tumor site and release ROS in response to the decreased pH value of TME, exerting ideal antitumor effects both in vitro and in vivo by activating the mitochondria-mediated apoptosis pathway. Simultaneously, this nanoplatform caused no detectable damage to normal tissues. Conclusions: After loading into the above nanocomposite, the free CaO2 without a significant antitumor effect can exert excellent antitumor efficacy by responsively releasing ROS under the acidic TME to induce the mitochondria-mediated apoptosis via remarkable oxidative stress and simultaneously minimize damages to normal tissues. The current study presents a new concept of "efficacy-shaping nanomedicine" for the tumor-selective treatment of prostate cancer.

Dataset Information

An "all-in-one" antitumor and anti-recurrence/metastasis nanomedicine with multi-drug co-loading and burst drug release for multi-modality therapy.

Publications

An "all-in-one" antitumor and anti-recurrence/metastasis nanomedicine with multi-drug co-loading and burst drug release for multi-modality therapy.

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