Self-Assembled Micelles Composed of Doxorubicin Conjugated Y-Shaped PEG-Poly(glutamic acid)2 Copolymers via Hydrazone Linkers

Abstract

Abstract:In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) 2 and linear copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose-and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y-shaped PEG-(polypeptide) 2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher OPEN ACCESSMolecules 2014, 19 11916 cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems.

The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model

“…Over the past few decades, there has been increasing interest in the potential use of NPs as delivery vehicles for chemotherapeutic drugs, and the studies have demonstrated that these nanocarriers can significantly enhance the anti-tumor efficiency of various chemotherapeutic drugs and also reduce or overcome the drug resistance of tumor cells [19][20][21][22].…”

Development of tailored SPION-PNIPAM nanoparticles by ATRP for dually responsive doxorubicin delivery and MR imaging

“…S4 (ESI †), free Dox rapidly passed through the cell membrane and entered into the cell nuclei even in 2.5 h and at low dose which increases dramatically with incubation time and dose. 46,47 Owing to its hydrophobic anthracycline backbone and also very small size, Dox can pass through the cell and also nuclear membrane by diffusion which is driven by a concentration gradient across the membranes. 48,49 SPION-PNIPAM-Dox nanoparticles, on the other hand, are very efficiently internalized by endocytosis but cannot enter the nucleus.…”

Self-assembling prodrugs

“…87 Here, DOX was conjugated to a branched PEG- b -P(Glu) 2 copolymer via hydrazone linkages (Figure 7b). Noted differences between the branched PDCs and their linear counterparts include smaller micellar diameters (166 vs 231 nm) and a more rapid drug release rate for the branched architecture.…”

“…Panel (a) was adapted from reference [86] with permission from the American Chemical Society (ACS), copyright 2013. Panel (b) was adapted from reference [87] with permission from the Multidisciplinary Digital Publishing Institute (MDPI), copyright 2014. Panel (c) was adapted from reference [88] with permission from ACS, copyright, 2016.…”