A zwitterionic polypeptide nanocomposite with unique NIR-I/II photoacoustic imaging for NIR-I/II cancer photothermal therapy.

The second near infrared photoacoustic imaging (NIR-II PAI) and photothermal therapy (NIR-II PTT) have attracted wide interest in cancer theranostics because of maximum permission exposure (MPE), deep penetration, and lower scattering and background noise compared to NIR-I counterparts; however, it is imperative to develop biocompatible nanomaterials having NIR-II response. By utilizing multivalent Au-S coordination bonds, we constructed a zwitterionic polypeptide nanocomposite of PMC@AuNP with a suitable size of 48 ± 2 nm, which possessed a strong and broad absorbance at 650-1100 nm and an excellent photothermal conversion efficiency of 49.5%. In vitro biological studies demonstrated that NIR-II PTT within MPE was more effective than NIR-I PTT beyond MPE. Along with X-ray computed tomography and photothermal imaging functions, PMC@AuNP in vivo presented unique NIR-I/II PAI with 2.6-5.9 times signal enhancement compared to the contrast. By single dose and NIR-II irradiation (1064 nm, 1 W cm-2, 10 min), NIR-II PTT within MPE completely eradicated MCF-7 tumors without tissue damage and tumor recurrence within 24 days, inducing a better antitumor efficacy than NIR-I PTT beyond MPE. Importantly, this study provides an innovative method for the fabrication of biocompatible zwitterionic polypeptide nanocomposites with unique NIR-I/II PAI and NIR-II PTT attributes, thus holding great potential for precise cancer theranostics and further clinical transitions.