The tumor microenvironment (TME) is characterized by low pH,
hypoxia, and infiltrated tumor-associated macrophages (TAMs). Therefore, regulation of TAMs polarization into anti-
tumor M1 phenotype and meanwhile alleviation of the
hypoxia in TME are expected to improve anti-
tumor therapeutic efficacy. To this end, a novel in situ
injectable nano-complexed
hydrogel was developed in this study for combining
tumor therapy. Thereunto,
hyaluronic acid modified transfersomes loaded with
chlorogenic acid functioned to reverse M2 type into M1 type via CD44 mediated internalization, the nanomedicine was entrapped in Schiff-based crosslinked
injectable hydrogel (fabricated with
carboxymethyl chitosan and oxidized
dextran) whose linkage was labile to the acidic TME for controlled drug release. Moreover,
catalase was integrated in the
hydrogel enabling to convert
hydrogen peroxide in TME into dissolved
oxygen and alleviate tumor hypoxia. The multifunctional nano-complexed
injectable hydrogel was verified to efficiently inhibit
tumor growth through synergetic effects of
hypoxia alleviation and TAMs polarity regulation.