Smart Nanoreactors for pH-Responsive Tumor Homing, Mitochondria-Targeting, and Enhanced Photodynamic-Immunotherapy of Cancer

Abstract

Photodynamic therapy (PDT) is an oxygen-dependent light-triggered noninvasive therapeutic method showing many promising aspects in cancer treatment. For effective PDT, nanoscale carriers are often needed to realize tumor-targeted delivery of photosensitizers, which ideally should further target specific cell organelles that are most vulnerable to reactive oxygen species (ROS). Second, as oxygen is critical for PDT-induced cancer destruction, overcoming hypoxia existing in the majority of solid tumors is important for optimizing PDT efficacy. Furthermore, as PDT is a localized treatment method, achieving systemic antitumor therapeutic outcomes with PDT would have tremendous clinical values. Aiming at addressing the above challenges, we design a unique type of enzyme-encapsulated, photosensitizer-loaded hollow silica nanoparticles with rationally designed surface engineering as smart nanoreactors. Such nanoparticles with pH responsive surface coating show enhanced retention responding to the acidic tumor microenvironment and are able to further target mitochondria, the cellular organelle most sensitive to ROS. Meanwhile, decomposition of tumor endogenous HO triggered by those nanoreactors would lead to greatly relieved tumor hypoxia, further favoring in vivo PDT. Moreover, by combining our nanoparticle-based PDT with check-point-blockade therapy, systemic antitumor immune responses could be achieved to kill nonirradiated tumors 1-2 cm away, promising for metastasis inhibition.

Immunomodulatory Nanosystems

“…Song et al designed a nanoparticle formed by photosensitizer PpIX and IDO inhibitor 1-methyl-Trp (1MT), connected by a caspase-sensitive peptide sequence. [161] Catalase, a H 2 O 2 -sensitive enzyme, and a photosensitizer Ce6 were loaded into a hollow silica nanoplatform as nanoreactor. Simultaneously, the elevated production of caspase-3 in apoptosis tumor cells liberated 1MT to block the IDO pathway and averted the immunosuppressive TME.…”

“…Reproduced with permission [161]. A) Synthetic process of DPEG-coating mitochondria-targeting nanoreactor loaded with catalase and Ce6, and schematic depiction of using nanoreactor to improve PDT process.…”

Enhancing Triple Negative Breast Cancer Immunotherapy by ICG‐Templated Self‐Assembly of Paclitaxel Nanoparticles

“…[10][11][12][13][14][15][16] Thus, complementary approaches to enhance the immunogenicity and reverse the ITM remain a formidable challenge for improving immunotherapy of TNBC. [21][22][23][24][25][26] However, combination immu notherapy suffers from the distinct chemophysical properties and incon sistent pharmacokinetic profiles of the different immune modulators. [21][22][23][24][25][26] However, combination immu notherapy suffers from the distinct chemophysical properties and incon sistent pharmacokinetic profiles of the different immune modulators.…”

Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis

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