Abstract
BackgroundSince the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors.ResultsIn this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions.ConclusionsThis approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.
Highlights
Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors
It is well known that cancer cells exist at different stages in the cell cycle for the heterogeneity of a tumor and different antitumor drugs have diverse inhibited mechanisms at varying stages of the cell cycle [6, 7]
The pointed-end, 10-hydroxycamptothecine (HCPT) nanoneedles with an average length of 5 μm were internalized much more rapidly and efficiently by three types of cancer cells than the nanorods with the same size and the nanospheres with a much smaller size of 150 nm [37]. We developed both methotrexate and 10-hydroxycamptothecine loaded nanoneedles (DDNDs) with high drug loading, targeting and imaging properties
Summary
Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors. Duo to the rapid development of the drug resistance in cancer cells [1, 2], the use of a single agent often fails to achieve the all-right therapeutic efficacy. To overcome this problem and improve anticancer efficacy, co-delivery of multifunctional agents is a promising strategy, which have received considerable research interest in cancer therapy [3,4,5]. The discussion of dual drug loaded nanostructures could be classified into the nanoparticle-based and carrier-free drug delivery systems. In spite of the improved properties, the low drug loading is the major shortcoming of carrier-based drug delivery systems. The concentration of research has been focused on how to combine the advantages of the two systems
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