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

Z Wang, L Wang, Neeraj Prabhakar, Y Xing, Jessica Rosenholm, J Zhang, K Cai

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

31 Citeringar (Scopus)
29 Nedladdningar (Pure)

Sammanfattning

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.

OriginalspråkOdefinierat/okänt
Sidor (från-till)416–428
TidskriftActa Biomaterialia
Volym86
DOI
StatusPublicerad - 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Nyckelord

  • siRNA
  • Nanomedicine
  • Photothermal effect
  • Porous materials

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