In:
Advanced Therapeutics, Wiley, Vol. 5, No. 8 ( 2022-08)
Abstract:
Pulmonary metastases pose treatment challenges for many cancers, including triple‐negative breast cancer (TNBC). A novel suicide gene and therapeutic microRNAs (miRs) combination therapy against lung metastases in vivo is tested in mouse models after intranasal delivery using nontoxic gold nanoparticles (AuNPs) formulated to carry these molecular therapeutics. AuNPs coated with chitosan‐β‐cyclodextrin (CS‐CD) are used and functionalized with a urokinase plasminogen activator (uPA) peptide to carry triple cancer suicide genes (thymidine kinase‐p53‐nitroreductase: TK‐p53‐NTR) plus therapeutic miRNAs (antimiR‐21, antimiR‐10b and miR‐100). Three AuNPs are synthesized: 20 nm gold nanodots (AuND), and 20 nm or 50 nm nanostars (AuNS), all surface coated with CS‐CD using a microfluidic‐optimized method. These positively charged AuNP‐CS‐CD cores are sequentially coated with synthetic miRNAs followed by TK‐p53‐NTR via electrostatic interactions, and uPA peptide is added through CD‐adamantane hostguest chemistry. Transfection efficiency comparisons for different AuNPs shows 50 nm AuNS allows ≈4.16‐fold higher gene transfection than other AuNPs. Intranasal delivery of uPA‐AuNS‐TK‐p53‐NTR‐microRNAs NPs (pAuNS@TK‐p53‐NTR‐miRs) in mice predominantly accumulates in lungs and facilitates ganciclovir and CB1954 prodrug‐mediated gene therapy against TNBC lung metastases. This new nanosystem can serve as an adaptable‐across‐cancer‐type, facile, and clinically scalable platform to allow future inhalational suicide gene‐miR combination therapy for patients harboring pulmonary metastases.
Type of Medium:
Online Resource
ISSN:
2366-3987
,
2366-3987
DOI:
10.1002/adtp.202200018
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2920320-X