Perfluorocarbon@Porphyrin Nanoparticles for Tumor Hypoxia Relief to Enhance Photodynamic Therapy against Liver Metastasis of Colon Cancer

Abstract

Photodynamic therapy (PDT) shows great promise for the treatment of colon cancer. However, practically, it is a great challenge to use a nanocarrier for the codelivery of both the photosensitizer and oxygen to improve PDT against PDT-induced hypoxia, which is closely related to tumor metastasis. Hence, an effective strategy was proposed to develop an oxygen self-supplemented PDT nanocarrier based on the ultrasonic dispersion of perfluorooctyl bromide (PFOB) liquid into the preformed porphyrin grafted lipid (PGL) nanoparticles (NPs) with high porphyrin loading content of 38.5%, followed by entrapping oxygen. Interestingly, the orderly arranging mode of porphyrins and alkyl chains in PGL NPs not only guarantees a high efficacy of singlet oxygen generation but also reduces fluorescence loss of porphyrins to enable PGL NPs to be highly fluorescent. More importantly, PFOB liquid was stabilized inside PGL NPs with an ultrahigh loading content of 98.15% due to the strong hydrophobic interaction between PGL and PFOB molecules, facilitating efficient oxygen delivery. Both in vitro and in vivo results demonstrated that the obtained O 2 @PFOB@PGL NPs could act as a prominent oxygen reservoir and effectively replenish oxygen into the hypoxic tumors with no need for external stimulation, conducive to augmented singlet oxygen generation, hypoxia relief, and subsequent downregulation of COX-2 expression. As a result, the use of O 2 @PFOB@PGL NPs for hypoxia relief dramatically inhibits tumor growth and liver metastasis in an HT-29 colon cancer mouse model. In addition, the O 2 @ PFOB@PGL NPs could serve as a bimodal contrast agent to enhance fluorescence and CT imaging, visualizing nanoparticle accumulation to guide the subsequent laser irradiation for precise PDT.

Photosensitizer Nanoparticles Boost Photodynamic Therapy for Pancreatic Cancer Treatment

“…By rational design of the PS encapsulation, PSs can be loaded with very high loading content while avoiding self-quenching [31][32][33]. Liang et al fabricated a series of PS-loaded nanoparticles based on porphyrin-grafted lipid (PGL) [32,34,35]. The porphyrin molecules can be loaded in the PGL nanoparticles with a drug loading as high as 38.45% [32].…”

Combining Photothermal‐Photodynamic Therapy Mediated by Nanomaterials with Immune Checkpoint Blockade for Metastatic Cancer Treatment and Creation of Immune Memory

“…O 2 (e.g., MnO 2 nanoparticles [58] ) or by incorporating oxygen carriers in the nanoformulations (e.g., perfluorocarbons [59] ). For instance, Huang and co-workers verified that mice treated with cancer cell membrane coated Fe 3 O 4 nanoparticles incorporating indocyanine green (ICG) plus NIR light display decreased levels of hypoxia-inducible factor 1-α in the tumor, indicating that the nanomaterials' mediated PTT could relieve tumor hypoxia.…”

“…The photothermal effect mediated by nanomaterials can improve the blood flow to the tumor site, improving tumor oxygenation. [ 56,57 ] Tumor hypoxia relief can also be achieved by engineering nanomaterials that can decompose H 2 O 2 into O 2 (e.g., MnO 2 nanoparticles [ 58 ] ) or by incorporating oxygen carriers in the nanoformulations (e.g., perfluorocarbons [ 59 ] ). For instance, Huang and co‐workers verified that mice treated with cancer cell membrane coated Fe 3 O 4 nanoparticles incorporating indocyanine green (ICG) plus NIR light display decreased levels of hypoxia‐inducible factor 1‐α in the tumor, indicating that the nanomaterials’ mediated PTT could relieve tumor hypoxia.…”

Nanomaterials for Tumor Hypoxia Relief to Improve the Efficacy of ROS-Generated Cancer Therapy

“…In recent years, an artificial blood product, perfluorocarbon (PFC) compounds with good biocompatibility and high oxygen dissolving ability, has been extensively used as O 2 carriers to modulate the hypoxic TME (Squires, 2002;Lee et al, 2015;Que et al, 2016;Liang et al, 2020). By loading a near-infrared photosensitizer (IR780) into PFCs nanodroplets, Cheng et al (2015) developed an oxygen self-enriching PDT (Oxy-PDT) nanoplatform (Figure 1C).…”