Steric Protected and Illumination‐Activated Tumor Targeting Accessory for Endowing Drug‐Delivery Systems with Tumor Selectivity

Abstract

Here, an ABA‐typed polymer, octadecyl‐polyethylene glycol (biotin)‐(o‐nitrobenzyl)‐octadecyl ester (CPB‐p‐C) with an o‐nitrobenzyl group inserted between polyethylene glycol (PEG) and octadecyl ester is synthesized as an illumination‐activated tumor targeting accessory for micelle‐based drug carriers. The functional accessory can form a flower‐like structure with folded PEG segments in aqueous solution to hide targeting biotin ligands in the core of the mixed micelle. Thus the specific binding between biotin and avidin can be suppressed by the steric hindrance of PEG shell. Upon illumination, the flower‐like structure of CPB‐p‐C is destroyed due to the cleavage of the o‐nitrobenzyl group and the biotin moieties are exposed on the surface of the micelle through the stretching process of PEG segments, generating ligand‐receptor‐mediated targeted delivery. By confocal laser scanning microscopy and flow cytometry, the illumination‐activated, tumor‐targeting delivery is studied. The influence of the amount of functional accessory in the mixed micelle on the targeting property is investigated and the optimal amount of CPB‐p‐C to achieve less side effects and better illumination activated tumor targeting activity is identified. The observed properties of CPB‐p‐C qualify it as a promising functional accessory to endow traditional drug‐delivery systems with tumor selectivity.

Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization

“…For example, an UV light responsive ONB group was inserted between hydrophilic PEG and hydrophobic octadecyl ester as a linker to synthesize an ABA‐typed amphiphilic polymer C 18 ‐PEG‐biotin‐photo site‐C 18 (CPB‐ p ‐C), which can form a flower‐like structure for the surface functionalization of Pluronic P 123 micelles (P 123 ). Biotin is bound by octadecyl ester and hidden by folded PEG chains . Upon UV irradiation triggered cleavage of the ONB groups, the flower‐like structure of the functional accessory will be destroyed and thus the biotin molecules will be popped up to the surface of micelles, resulting in receptor‐mediated specific targeted delivery ( Figure A).…”

Photoresponsive nanoparticles for drug delivery

“…Irradiation with a UV lamp cleaved the o -nitrobenzyl moiety, exposing the peptide still tethered to the particle surface by PEG. Biotin ligands on polymeric nanoparticles have been controlled by UV light by a similar strategy [180]. …”

Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine

“…Biotin (vitamin B7) is a small molecule, which is strongly bound by the tetrameric protein avidin (almost irreversibly), and receptors are overexpressed on certain cell lines in humans (HeLa, murine leukemia and others). In 2013, Li and co‐workers implemented an approach using a loop‐type structure containing biotin 8 (see Figure ) and a photocleavable 2‐nitrobenzyl unit with a hydrophobic anchor at both sides (similar to the previously mentioned work of Löwik) . The loop was then subjected to micelle formation with pluronic P 123 (a polymeric material based on PEG and PPG) resulting in a material bearing surface loops, subsequently opened by the action of polychromatic UV light (penetration depth: ∼0.05–0.2 mm).…”

“…In 2013, Li and co-workersi mplemented an approachu sing al oop-type structure containing biotin 8 (see Figure 7) and ap hotocleavable 2nitrobenzyl unit with ahydrophobic anchoratboth sides (similar to the previously mentioned work of Lçwik). [100] The loop was then subjected to micelle formation with pluronic P 123 (a polymericm aterialb ased on PEG and PPG) resulting in am aterial bearing surface loops,s ubsequently openedb yt he action of polychromatic UV light (penetration depth:~0.05-0.2 mm). The authors were able to induce ap hototriggered cellular uptake in HeLa, and liberated doxorubicin into the cells, inducing cell death with high efficiencies and selectivities.…”