Photodynamic
therapy (PDT), is a rising star for suppression of in situ and metastatic tumors, yet it is impeded by low
ROS production and off-target phototoxicity. Herein, an aggregation
degree editing strategy, inspired by gene editing, was accomplished
by the coordination of an aggregation degree editor, p(MEO2MA160-co-OEGMA40)-b-pSS30 [POEGS; MEO2MA = 2-(2-methoxyethoxy)ethyl methacrylate, OEGMA = oligo(ethylene
glycol) methacrylate; pSS = poly(styrene sulfonate)]
and indocyanine green (ICG) to nontoxic Mg2+, forming an
ICG discretely loaded nanoaggregate (ICG-DNA). Optimization of the
ICG aggregation degree [POEGS/ICG (P/I) = 6.55] was achieved by tuning
the P/I ratio, alleviating aggregation-caused-quenching (ACQ) and
photobleaching concurrently. The process boosts the PDT efficacy,
spurring robust immunogenic cell death (ICD) and systemic antitumor
immunity against primary and metastatic immunogenic “cold”
4T1 tumors via intratumoral administration. Moreover,
the temperature-sensitive phase-transition property facilitates intratumoral
long-term retention of ICG-DNA, reducing undesired phototoxicity to
normal tissues; meanwhile, the photothermal-induced tumor oxygenation
further leads to an augmented PDT outcome. Thus, this simple strategy
improves PDT efficacy, boosting the singlet oxygen quantum yield (Φ
Δ)-dependent ICD effect and systemic
antitumor responses via local treatment.