CaP coated mesoporous polydopamine nanoparticles with responsive membrane permeation ability for combined photothermal and siRNA therapy

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Wang Z, Wang L, Prabhakar N, Xing Y, Rosenholm JM, Zhang J, Cai K
Förläggare: Elsevier
Publiceringsår: 2019
Tidskrift: Acta Biomaterialia
Volym: 86
Artikelns första sida, sidnummer: 416
Artikelns sista sida, sidnummer: 428
ISSN: 1742-7061


Abstrakt

Combined photothermal and gene therapy provides a promising
modality toward cancer treatment, yet facile integration and controlled
codelivery of gene payloads and photothermal conversion agents (PTCAs)
remains a great challenge. Inspired by the robust wet adhesion of marine
mussels, we present a rationally designed nanosystem constructed by using hybrid mesoporous polydopamine nanoparticles (MPDA) with sub-100 nm sizes and a high photothermal conversion efficiency of 37%. The surface of the particles were modified with tertiary amines by the facile Michael addition/Schiff base reactions of PDA to realize high siRNA loading capacity (10 wt%). Moreover, a successful calcium phosphate (CaP) coating via biomineralization was constructed on the cationic nanoparticle to prohibit premature release of siRNA. The CaP coating underwent biodegradation
in weakly-acidic subcellular conditions (lysosomes). The synergistic
integration of tertiary amines and catechol moieties on the subsequently
exposed surfaces was demonstrated to feature the
destabilization/disruption ability toward model cellular membranes via
the greatly enhanced interfacial adhesion and interactions.
Consequently, sufficient permeability of lysosomal membranes, and in
turn, a high lysosomal escape efficiency, was realized, which then
resulted in high gene silencing efficiencies via sufficient cytosolic
delivery of siRNA. When an efficient knocking down (65%) of survivin (an inhibitor of apoptosis proteins) was combined with a subsequent photothermal ablation, remarkably higher therapeutic efficiencies were observed both in vitro and in vivo,
as compared with monotherapy. The system may help to pave a new avenue
on the utilization of bio-adhesive surfaces for handling the obstacles
of combined photothermal and gene therapy.


Nyckelord

Nanomedicine, Photothermal effect, Porous materials, siRNA


Dokument


Senast uppdaterad 2020-29-03 vid 08:53