The present study investigated the concurrent delivery
of antineoplastic
drug, doxorubicin, and HER2 siRNA through a targeted theranostic metallic
gold nanoparticle designed using polysaccharide, PSP001. The as-synthesized
HsiRNA@PGD NPs were characterized in terms of structural, functional,
physicochemical, and biological properties. HsiRNA@PGD NPs exposed
adequate hydrodynamic size, considerable ζ potential, and excellent
drug/siRNA loading and encapsulation efficiency. Meticulous exploration
of the biocompatible dual-targeted nanoconjugate exhibited an appealing
biocompatibility and pH-sensitive cargo release kinetics, indicating
its safety for use in clinics. HsiRNA@PGD NPs deciphered competent
cancer cell internalization, enhanced cytotoxicity mediated via the
induction of apoptosis, and excellent downregulation of the overexpressing
target HER2 gene. Further in vivo explorations in
the SKBR3 xenograft breast tumor model revealed the appealing tumor
reduction properties, selective accumulation in the tumor site followed
by significant suppression of the HER2 gene which contributed to the
exclusive abrogation of breast tumor mass by the HsiRNA@PGD NPs. Compared
to free drugs or the monotherapy constructs, the dual delivery approach
produced a synergistic suppression of breast tumors both in
vitro and in vivo. Hence the drawings from
these findings implicate that the as-synthesized HsiRNA@PGD NPs could
offer a promising platform for chemo-RNAi combinational breast cancer
therapy.