As a novel treatment
modality of tumors, hypothermal hyperthermia
employed relatively lower temperature (<45 °C) to damage cancer
cells with mild toxicity to normal tissues. However, beyond that inducible
heat resistance of tumor cells, the discounted therapeutic effect
of low temperature hyperthermia was also ascribed to poor penetration
of exogenous light stimulation and low accumulation of photothermal
agents in tumor sites. Herein, we constructed a multifunctional in
situ hydrogel of sodium alginate (ALG) via Ca2+ coordinated
with ALG to encapsulate the photothermal agent of Ink and azo initiator
of 2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride
(AIPH) for effective tumor treatment. The designed ALG hydrogel was
used to improve the therapeutic effect by increased accumulation of
Ink and AIPH and avoid potential side-effects caused by the unexpected
spread to the surrounding normal tissues. After injection, local low
temperature stimulation was generated with near-infrared-II irradiation
by a 1064 nm laser, triggering rapid decomposition of AIPH to produce
alkyl radicals. The synergistic low temperature photothermal therapy
and cytotoxic-free radicals enhanced the apoptosis of tumor cells
via physical heat damage and lipid peroxidation. Thus, remarkable
inhibition of tumor growth was observed in a subcutaneous colorectal
cancer with negligible side effects. Furthermore, the formulation
could also exert strong photoacoustic signals, which were utilized
to monitor the stability of the composite hydrogel.