Well‐Defined, Reversible Boronate Crosslinked Nanocarriers for Targeted Drug Delivery in Response to Acidic pH Values and cis‐Diols

Abstract

Demand and deliver: Micelles reversibly crosslinked by boronate esters (see scheme) show in vitro and in vivo stability, and thus minimize premature drug release under physiological conditions. After reaching the tumor sites, drug (stars in scheme) release is activated by cleavage of the boronate esters by the acidic conditions around the tumor or in the target cells, or by the administration of mannitol.

Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer

“…We recently reported on the development of disulfide or boronate-catechol cross-linked nanomicelles 23,24 that are much more stable than the non-crosslinked micelles reported here. The main advantage of crosslinked micelles is that premature drug release in the circulation can be minimized.…”

“…One explanation for this is that the current nanomicelle formulation is not stable in blood and that the nanomicelles disassemble partially and the loaded drug begins to release from the nanomicelles immediately after in vivo administration and diffusion into normal organs, resulting in a rapid decrease of 14 C-PTX in the circulation. 23,24 In contrast, the 125 I-telodendrimers, even if coming from dissociated nanomicelles, still remain in the blood circulation for a longer time, contributing to a much higher radioactive signal in the blood during the 24 hours post injection.…”

pH-responsive glycol chitosan-cross-linked carboxymethyl-β-cyclodextrin nanoparticles for controlled release of anticancer drugs

“…1 To reduce the cytotoxicity and improve the therapeutic efficacy of these drugs, several environmentally responsive nanoparticle (NP)-based drug-delivery systems [2][3][4] have been explored in recent decades. Among them, pH-responsive NPs have been extensively investigated 2 because of the slightly lower pH (~4.0-6.8) [4][5][6] of extracellular fluids and intracellular vesicles of tumors. For instance, She et al 7 made pH-responsive NPs of polyethylene glycosylated peptide dendron-doxorubicin conjugates for cancer therapy.…”

“…6,32 If the carrier can release the drug in an acidic environment but retain it under physiological conditions, it will improve the drug-targeting action and facilitate drug release, decreasing side effects and increasing drug bioavailability.…”

“…The synthesized CMβ-CDs were composed of β-CD-(CH 2 COOH) 2 , β-CD-(CH 2 COOH) 3 , β-CD-(CH 2 COOH) 4 , β-CD-(CH 2 COOH) 5 , β-CD-(CH 2 COOH) 6 , and β-CD-(CH 2 COOH) 7 indicating that more than one carboxymethyl combined with β-CD. One reacted with GCS, but there were also many free carboxymethyl groups around the CMβ-CD cavity.…”