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Abstract
BackgroundPoor targeting and penetration of chemotherapy drugs in solid tumors, and the development of resistance to chemotherapeutic agents are currently hindering the therapy of breast cancer; meanwhile, breast cancer metastasis is one of the leading causes of death in breast cancer patients. With the development of nanotechnology, nanomaterials have been widely used in tumor therapy.ResultsA multi-functional nano-platform containing gambogic acid (GA) and paclitaxel (PTX) was characterized by a small size, high encapsulation efficiency, slow release, long systemic circulation time in vivo, showed good targeting and penetrability to tumor tissues and tumor cells, and exhibited higher anti-tumor effect and lower systemic toxicity in BALB/c mice bearing 4T1 tumor. GA not only overcame the multidrug resistance of PTX by inhibiting P-glycoprotein (P-gp) activity in MCF-7/ADR cells, but also inhibited MDA-MB-231 cells migration and invasion, playing a crucial role in preventing and treating the lung metastasis of breast cancer caused by PTX; meanwhile, the synergistic anti-tumor effect of GA and PTX has also been verified in vitro and in vivo experiments.ConclusionOur data described the better recognition and penetration of tumor cells of R9dGR-modified versatile nanosystems containing GA and PTX, which exerted one stone three birds clinical therapeutic efficacy of multifunctionality.
Highlights
Poor targeting and penetration of chemotherapy drugs in solid tumors, and the development of resistance to chemotherapeutic agents are currently hindering the therapy of breast cancer; breast cancer metastasis is one of the leading causes of death in breast cancer patients
Determination of combination index The anti-proliferative effects of gambogic acid (GA) and PTX were determined with the Cell Counting Kit 8 (CCK-8) assay in 4T1 cell lines after 24 h of drug treatment, and the interaction between GA and PTX was quantified by measuring the Combination index (CI)
The results showed that CI values of different combinations of drug doses ranged from 0.240 to 1.436 as seen in Table 1 and Fig. 1c, which showed that no synergistic cytotoxiciity was observed in e, f, h, l (CI>1)
Summary
Poor targeting and penetration of chemotherapy drugs in solid tumors, and the development of resistance to chemotherapeutic agents are currently hindering the therapy of breast cancer; breast cancer metastasis is one of the leading causes of death in breast cancer patients. As a malignant disease, is one of the leading causes of death in the world [1, 2]. The poor targeting and permeability of chemotherapy drugs in solid tumors hinders the treatment of breast cancer. NLCs, as mixtures of solid and liquid lipids, are characterized by higher encapsulation efficiency, excellent drug-loading capacity, better stabilization, sustained release properties, and the long resident time in blood [4]. NLCs have dominant position in the treatment of diseases in special fields, including cancer [5]
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