Multi-functional self-fluorescent unimolecular micelles for tumor-targeted drug delivery and bioimaging

Abstract

A novel type of self-fluorescent unimolecular micelle nanoparticle (NP) formed by multi-arm star amphiphilic block copolymer, Boltron® H40 (H40, a 4th generation hyperbranched polymer)-biodegradable photo-luminescent polymer (BPLP)-poly(ethylene glycol) (PEG) conjugated with cRGD peptide (i.e., H40-BPLP-PEG-cRGD) was designed, synthesized, and characterized. The hydrophobic BPLP segment was self-fluorescent, thereby making the unimolecular micelle NP self-fluorescent. cRGD peptides, which can effectively target αvβ3 integrin-expressing tumor neovasculature and tumor cells, were selectively conjugated onto the surface of the micelles to offer active tumor-targeting ability. This unique self-fluorescent unimolecular micelle exhibited excellent photostability and low cytotoxicity, making it an attractive bioimaging probe for NP tracking for a variety of microscopy techniques including fluorescent microscopy, confocal laser scanning microscopy (CLSM), and two-photon microscopy. Moreover, this self-fluorescent unimolecular micelle NP also demonstrated excellent stability in aqueous solutions due to its covalent nature, high drug loading level, pH-controlled drug release, and passive and active tumor-targeting abilities, thereby making it a promising nanoplatform for targeted cancer theranostics.

Biodegradation and Toxicity of Protease/Redox/pH Stimuli-Responsive PEGlated PMAA Nanohydrogels for Targeting Drug delivery

“…However, we found that the hydrophobic domains introduced in nanohydrogels could form hydrophobic interactions with the hydrophobic drugs, thus greatly increasing the drug loading efficency. [18][19][20][21] Just as we known, the drugs with different anticancer 4 mechanisms will work at different growth stages of tumor cells, then loading of multiple drugs in one drug carrier can act synergistically to gain superior response and patient survival rate. 22,23 Tumor cells usually have unique environment including lower pH and higher redox potential compared with normal cells, which can be exploited as stimuli triggers for responsive drug release.…”

KE108-conjugated unimolecular micelles loaded with a novel HDAC inhibitor thailandepsin-A for targeted neuroendocrine cancer therapy

“…Hence, there is a need to develop strategies to enhance the in vivo stability of self-assembled drug nanocarriers. Unimolecular micelles formed by individual/ single multi-arm star amphiphilic block copolymer molecules exhibit excellent stability in vitro and in vivo due to their unique chemical structure and covalent nature [32–40]. These unique unimolecular micelles have been successfully used to deliver various compounds to tumor tissues in a targeted manner [32–40].…”

Periadventitial drug delivery for the prevention of intimal hyperplasia following open surgery

“…(3) NPs are highly customizable and can be readily tailored for controlled and sustained drug release[46]. (4) NPs can be produced with hydrophobic cores to harbor a hydrophobic drug, while a hydrophilic outer surface renders the drug-loaded NPs highly soluble[47]. (5) NPs can be fluorescently labeled, facilitating in vitro and in vivo imaging and localization[47].…”

“…(4) NPs can be produced with hydrophobic cores to harbor a hydrophobic drug, while a hydrophilic outer surface renders the drug-loaded NPs highly soluble[47]. (5) NPs can be fluorescently labeled, facilitating in vitro and in vivo imaging and localization[47]. (6) For targeting a specific tissue or cell population, the surface of the NP can be conjugated with targeting ligands[48, 49].…”

“…The “payload” that can be delivered ranges from small molecules, proteins/peptides, to nucleic acid (e.g., siRNAs and DNA). Recently, unimolecular micelle NPs, formed by individual/single multi-arm star amphiphilic block copolymer molecules, have gained more attention due to their excellent in vitro and in vivo stability, and chemical versatility including the ability of conjugating various types of targeting ligands [47, 57–59]. NPs conjugated with a specific type of targeting ligand can recognize its cognate receptor highly expressed on the surface of a specific population of cells allowing for preferential cellular uptake of targeted NPs.…”