Here, we construct a tumour microenvironment-responsive nanosystem, based on PEGylated polyethylenimine-coated gold nanoparticles, and utilise it to co-deliver all-trans retinoic acid (ATRA, an inducer of PSC quiescence) and siRNA targeting heat shock protein 47 (HSP47, a collagen-specific molecular chaperone) to re-educate PSCs.
In this review, we highlight the fundamental aspects of the interaction between HSP47 and collagen and the recent discoveries of the role of this chaperone in different types of malignant neoplasias.
Validation analysis by immunohistochemistry showed that HSP47 expression in patients with CRC and the number of HSP47-positive spindle cells in the tumor stroma were significantly higher compared with those in adjacent normal colonic mucosa, and the number of the latter cells increased with tumor progression.
HSP47 knockdown by siRNAs significantly decreased cell viability in vitro and tumor volume in vivo; moreover, it reduced the microvessel density (MVD) by CD31 immunohistochemistry in vivo.
Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin.
The enhanced targeting achieved with Ad5-Flag-LDS highlights a potential strategy for clinically applicable targeted gene therapy against HNSCC or any tumor type expressing Hsp47.