Decrease in Tumor Interstitial Pressure for Enhanced Drug Intratumoral Delivery and Synergistic Tumor Therapy

Abstract

Currently, one of the main reasons for the ineffectiveness of tumor treatment is that the abnormally high tumor interstitial pressure (TIP) hinders the delivery of drugs to the tumor center and promotes intratumoral cell survival and metastasis. Herein, we designed a “nanomotor” by in situ growth of Ag2S nanoparticles on the surface of ultrathin WS2 to fabricate Z-scheme photocatalytic drug AWS@M, which could rapidly enter tumors by splitting water in interstitial liquid to reduce TIP, along with O2 generation. Moreover, the O2 would be further converted to reactive oxygen species (ROS), accompanied by increased local temperature of tumors, and the combination of ROS with thermotherapy could eliminate the deep tumor cells. Therefore, the “nanomotor’’ could effectively reduce the TIP levels of cervical cancer and pancreatic cancer (degradation rates of 40.2% and 36.1%, respectively) under 660 nm laser irradiation, further enhance intratumor drug delivery, and inhibit tumor growth (inhibition ratio 95.83% and 87.61%, respectively), and the related mechanism in vivo was explored. This work achieves efficiently photocatalytic water-splitting in tumor interstitial fluid to reduce TIP by the nanomotor, which addresses the bottleneck problem of blocking of intratumor drug delivery, and provides a general strategy for effectively inhibiting tumor growth.

Nanotechnological strategies to increase the oxygen content of the tumor

“…Second, the tumor volume is constantly increasing. When the tumor volume increases to the oxygen diffusion limit (100–200 μm), the blood vessels cannot provide sufficient oxygen for the tissue cells ( Bennewith and Dedhar, 2011 ; Fu et al, 2022 ).…”

Enhancing the Treating Efficacy of Immunotherapy through the Restructure of Tumor Microenvironment

“…In addition, O 2 can be converted into ROS through photocatalysis and display strong cytotoxicity (Figure 7d). [ 124 ]…”

“…The levels of IFP in g) U14 tumors and h) PAN02 tumors administered with saline and AWS@ þ L groups. Reproduced with permission [124]. Copyright 2022, American Chemical Society.…”

2D Transition Metal Dichalcogenides for Photocatalysis

“…[43] Theoretically, several 2D TMDs-based heterojunction interfaces can be formed, according to the band alignments and directivity of electron transfer, including type I (straddling gap), type II (alternate gap), Z-scheme (alternate gap), type III (broken gap), and Schottky junction (or ohmic junction) (Figure 15a). [43] Among them, type II, [100,147,148] Zscheme, [32,36,[149][150][151] and Schottky junction [28,33,[152][153][154][155] (or ohmic junction [156] ) are energy band well matched. At these heterojunction interface (type II, Z-scheme, and Schottky junction or ohmic junction), photoinduced electrons or holes are transfer from one building block to another and enriched in different building block (as shown in Figure 15a).…”