Extravascular gelation shrinkage-derived internal stress enables tumor starvation therapy with suppressed metastasis and recurrence

Abstract

Despite the efficacy of current starvation therapies, they are often associated with some intrinsic drawbacks such as poor persistence, facile tumor metastasis and recurrence. Herein, we establish an extravascular gelation shrinkage-derived internal stress strategy for squeezing and narrowing blood vessels, occluding blood & nutrition supply, reducing vascular density, inducing hypoxia and apoptosis and eventually realizing starvation therapy of malignancies. To this end, a biocompatible composite hydrogel consisting of gold nanorods (GNRs) and thermal-sensitive hydrogel mixture was engineered, wherein GRNs can strengthen the structural property of hydrogel mixture and enable robust gelation shrinkage-induced internal stresses. Systematic experiments demonstrate that this starvation therapy can suppress the growths of PANC-1 pancreatic cancer and 4T1 breast cancer. More significantly, this starvation strategy can suppress tumor metastasis and tumor recurrence via reducing vascular density and blood supply and occluding tumor migration passages, which thus provides a promising avenue to comprehensive cancer therapy.

Targeting hypoxic tumor microenvironment in pancreatic cancer

“…In contrast to vascular normalizing strategies, starvation therapy engineered by an extravascular gelation shrinkage-derived internal stress strategy reduces vessel density, occludes blood supply and tumor migration passages, and induces hypoxia and apoptosis, thereby suppressing PANC-1 PC growth, metastasis, and recurrence [ 235 ]. Apart from squeezing and narrowing blood vessels by increasing extravascular pressure, tumor angiogenesis is targeted to realize starvation therapy as well.…”

Advances and trends of hydrogel therapy platform in localized tumor treatment: A review

“…Moreover, starving therapy also shows promising therapeutic property in prevention of cancer metastasis and recurrence. A novel extravascular chitosan/ mPEG‐Mal/pNIPAAm‐co‐AAc containing PEG‐SH‐modified gold nanorods composite hydrogel was reported, which acted by shrinking under NIR, thus decreasing the blood supply and vessel density in tumor area 169 . This particular therapeutic mechanism was confirmed in vivo PANC‐1 pancreatic cancer and 4T1 breast cancer animal experiment, with a low lung metastasis and recurrence rate.…”

Recent Advancements in Nanomedicine for ‘Cold’ Tumor Immunotherapy

“…With advancements in biomedical equipment, microinvasive PTT and PDT have received increasing attention owing to their accuracy and high efficiency during tumor destruction and during ROS-associated ICD induction [136][137][138][139]. For example, Zhang et al [140] proposed that the tumor starvation therapy performed by PTT-inducing gelation shrinkage could comprehensively suppress the tumor growth, whether the tumor is in situ, metastatic or recurrence.…”