期刊
SMALL
卷 18, 期 41, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202204732
关键词
diatomite nanoparticles; gene therapy; peptide nucleic acids; redox-responsive; surface chemistry
类别
资金
- Programma Operativo Nazionale-Attraction and Internetional Mobility (PON-AIM) RTDA_L1 [AIM 1873131-2]
- Sigrid Juselius Foundation
- Academy of Finland [331151]
- UMCG Research Funds
Redox-responsive silica drug delivery systems were synthesized using eco-friendly diatomite source to achieve on-demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, inhibiting immune check-point PD-1/PD-L1 in cancer cells. The systems showed safety and advantages in controlling and enhancing PNA release, paving the way for targeted immunotherapy.
Redox-responsive silica drug delivery systems are synthesized by aeco-friendly diatomite source to achieve on-demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, aiming to inhibit the immune check-point programmed cell death 1 receptor/programmed cell death receptor ligand 1 (PD-1/PD-L1) in cancer cells. The nanoparticles (NPs) are coated with polyethylene glycol chains as gatekeepers to improve their physicochemical properties and control drug release through the cleavable disulfide bonds (S-S) in a reductive environment. This study describes different chemical conditions to achieve the highest NPs' surface functionalization yield, exploring both multistep and one-pot chemical functionalization strategies. The best formulation is used for covalent PNA conjugation via the S-S bond reaching a loading degree of 306 +/- 25 mu g (PNA) mg(DNPs)(-1). These systems are used for in vitro studies to evaluate the kinetic release, biocompatibility, cellular uptake, and activity on different cancer cells expressing high levels of PD-L1. The obtained results prove the safety of the NPs up to 200 mu g mL(-1) and their advantage for controlling and enhancing the PNA intracellular release as well as antitumor activity. Moreover, the downregulation of PD-L1 observed only with MDA-MB-231 cancer cells paves the way for targeted immunotherapy.
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