Folate-modified poly(2-ethyl-2-oxazoline) as hydrophilic corona in polymeric micelles for enhanced intracellular doxorubicin delivery.

The transmembrane transport of drug loaded micelles to intracellular compartment is quite crucial for efficient drug delivery. In the current study, we investigated the cellular internalization and anticancer activity of doxorubicin loaded micelles with folate modified stealthy PEOz corona. Folate-decorated micelles incorporating doxorubicin were characterized for particle size, degree of folate decoration, drug loading content and encapsulation efficiency, morphology, and surface charge. The targeting capability and cell viability were assessed using HeLa, KB, A549 and MCF-7/ADR cell lines. In vitro study clearly illustrated the folate receptor (FR) mediated targeting of FA modified micelles to FR-positive human HeLa, KB and MCF-7/ADR cells, while specific delivery to FR-negative A549 cells was not apparently increased at the same experimental conditions. Cytotoxicity assay showed 60% and 58% decrease in IC50 values for HeLa and KB cells, while only a slight decrease for A549 cells, following treatment with folate modified formulations. The enhanced intracellular delivery of FA modified micelles in MCF-7/ADR cells was also observed. In vivo antitumor tests revealed DOX entrapped FA-PEOz-PCL micelles effectively inhibited the tumor growth and reduced the toxicity to mice compared with free DOX. The current study showed that the targeted nano-vector improved cytotoxicity of DOX and suggested that this novel PEOz endowed stealthy micelle system held great promise in tumor targeted therapy.

Qiu LY ，Yan L ，Zhang L ，Jin YM ，Zhao QH ... -  《-》

Folate-functionalized unimolecular micelles based on a degradable amphiphilic dendrimer-like star polymer for cancer cell-targeted drug delivery.

Cao W ，Zhou J ，Mann A ，Wang Y ，Zhu L ... -  《-》

Dual targeting folate-conjugated hyaluronic acid polymeric micelles for paclitaxel delivery.

A series of novel self-assembled hyaluronic acid derivatives (HA-C(18)) grafted with hydrophobic octadecyl moiety and further dual targeting folic acid-conjugated HA-C(18) (FA-HA-C(18)) were synthesized. With the increase in the degree of substitution of octadecyl group from 12.7% to 19.3%, the critical micellar concentration of HA-C(18) copolymers decreased from 37.3 to 10.0 μg/mL. Paclitaxel (PTX) was successfully encapsulated into the hydrophobic cores of the HA-C(18) and FA-HA-C(18) micelles, with encapsulation efficiency as high as 97.3%. The physicochemical properties of the polymeric micelles were measured by DLS, TEM and DSC. Moreover, in vitro release behavior of PTX was investigated by dialysis bag method and PTX was released from micelles in a near zero-order sustained manner. In vitro antitumor activity tests suggested PTX-loaded HA-C(18) and FA-HA-C(18) micelles exhibited significantly higher cytotoxic activity against MCF-7 and A549 cells compared to Taxol at a lower PTX concentration. The cellular uptake experiments were conducted by quantitative assay of PTX cellular accumulation and confocal laser scanning microscopy imaging of coumarin-6 labeled HA-C(18) and FA-HA-C(18) micelles in folate receptor overexpressing MCF-7 cells. Folate and CD44 receptor competitive inhibition studies performed by fluorescence microscopy imaging suggested intracellular delivery of HA-C(18) and FA-HA-C(18) micelles were efficiently taken up via CD44 receptor-mediated endocytosis. The folate receptor-mediated endocytosis further enhanced internalized amounts of FA-HA-C(18) micelles in MCF-7 cells, as compared with HA-C(18) micelles. The internalization pathways of PTX-loaded HA-C(18) and FA-HA-C(18) micelles might include clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis. Therefore, the present study suggested that HA-C(18) and FA-HA-C(18) copolymers as biodegradable, biocompatible and cell-specific targetable nanostructure carriers, are promising nanosystems for cellular and intracellular targeting delivery of hydrophobic anticancer drugs.

Liu Y ，Sun J ，Cao W ，Yang J ，Lian H ，Li X ，Sun Y ，Wang Y ，Wang S ，He Z ... -  《-》

Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor.

Lee ES ，Na K ，Bae YH 《JOURNAL OF CONTROLLED RELEASE》

In vivo antitumor activity of the folate-conjugated pH-sensitive polymeric micelle selectively releasing adriamycin in the intracellular acidic compartments.

Bae Y ，Nishiyama N ，Kataoka K 《BIOCONJUGATE CHEMISTRY》