Hydrophobic binding peptide-conjugated hybrid lipid-mesoporous silica nanoparticles for effective chemo-photothermal therapy of pancreatic cancer
Raj Kumar Thapa
Hanh Thuy Nguyen
Milan Gautam
Aarajana Shrestha
Eung Seok Lee
Sae Kwang Ku
Han-Gon Choi
Chul Soon Yong
Jong Oh Kim
10.6084/m9.figshare.5568079
https://tandf.figshare.com/articles/journal_contribution/Hydrophobic_binding_peptide-conjugated_hybrid_lipid-mesoporous_silica_nanoparticles_for_effective_chemo-photothermal_therapy_of_pancreatic_cancer/5568079
<p>Nanoparticle-based drug delivery systems are designed to reach tumor sites based on their enhanced permeation and retention effects. However, a lack of interaction of these nanoparticles with cancer cells might lead to reduced uptake in the tumors, which might compromise the therapeutic efficacy of the system. Therefore, we developed bortezomib and IR-820-loaded hybrid-lipid mesoporous silica nanoparticles conjugated with the hydrophobic-binding peptide, cyclosporine A (CsA), and referred to them as CLMSN/BIR. Upon reaching the tumor site, CsA interacts hydrophobically with the cancer cell membranes to allow effective uptake of the nanoparticles. Nanoparticles ∼160 nm in size were prepared and the stability of IR-820 significantly improved. High cellular uptake of the nanoparticles was evident with pronounced apoptotic effects in PANC-1 and MIA PaCa-2 cells that were mediated by the chemotherapeutic effect of bortezomib and the photothermal and reactive oxygen species generation effects of IR-820. An <i>in vivo</i> biodistribution study indicated there was high accumulation in the tumor with an enhanced photothermal effect in PANC-1 xenograft mouse tumors. Furthermore, enhanced antitumor effects in PANC-1 xenograft tumors were observed with minimal toxicity induction in the organs of mice. Cumulatively, these results indicated the promising effects of CLMSN/BIR for effective chemo-phototherapy of pancreatic cancers.</p>
2017-11-03 10:32:02
Bortezomib
hydrophobic-binding peptide
IR-820
pancreatic cancer
chemo-phototherapy