Nucleobase-crosslinked poly(2-oxazoline) nanoparticles as paclitaxel carriers with enhanced stability and ultra-high drug loading capacity for breast cancer therapy

• Main Authors: Si Dong (Author), Sheng Ma (Author), Hongyu Chen (Author), Zhaohui Tang (Author), Wantong Song (Author), Mingxiao Deng (Author)
• Format: Book
• Published: Elsevier, 2022-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1818-0876; 10.1016/j.ajps.2022.04.006
• Keywords: Poly(2-oxaozoline); Nanoparticles; Paclitaxel; Nucleobase-crosslinked; Murine breast cancer; Therapeutics. Pharmacology; RM1-950
• Source: Asian Journal of Pharmaceutical Sciences, Vol 17, Iss 4, Pp 571-582 (2022)

Poly(2-oxazoline) (POx) has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation, due to its excellent biocompatibility and self-assembly properties. The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers, however, tend to be insufficient. Herein, we report a strategy to prepare nucleobase-crosslinked POx nanoparticles (NPs) with enhanced stability and ultra-high paclitaxel (PTX) loading capacity for breast cancer therapy. An amphiphilic amine-functionalized POx (PMBEOx-NH2) was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly (2‑butyl‑2-oxazoline-co-2-butenyl-2-oxazoline) (PMBEOx). Complementary nucleobase-pairs adenine (A) and uracil (U) were subsequently conjugated to PMBEOx-NH2 to give functional POxs (POxA and POxU), respectively. Due to the nucleobase interactions formed between A and U, NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity (38.2%, PTX/POxA@U), excellent stability, and reduced particle size compared to the uncross-linked PTX-loaded NPs (PTX/PMBEOx). Besides the prolonged blood circulation and enhanced tumor accumulation, the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx, thus leading to a higher tumor suppression rate in two murine breast cancer models (E0711 and 4T1). These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.