Oxygen-Self-Supplying and HIF-1α-Inhibiting Core–Shell Nanosystem for Hypoxia-Resistant Photodynamic Therapy

Abstract

Extreme hypoxia together with the expression of hypoxia-inducible factor-1α (HIF-1α) represents a significant barrier against the effective photodynamic therapy (PDT) of tumor. To mitigate these issues, we created a core− shell nanosystem that can simultaneously alleviate tumor hypoxia and suppress the expression of HIF-1α to combat tumor resistance against PDT. Specifically, a carrier-free, dualdrug nanocore was formed by the self-assembly of hydrophobic photosensitizer (chlorin e6, Ce6) and rapamycin (RAP), and then the surface was coated by a layer of metal− organic frameworks (MOFs) to load catalase, reaching an overall drug loading of ∼60%. In such system, catalase acted as oxygen-self-supplier to catalyze the decomposition of tumor-abundant H 2 O 2 into O 2 , and the sustained release of RAP downregulated HIF-1α, which collectively potentiated the PDT efficacy against tumor. The nanosystem could passively accumulate into tumor, realize in situ oxygen generation and HIF-1α inhibition in tumor tissue, and thus exhibit strong PDT effect toward highly hypoxia tumor. This work provides a highly promising nanoplatform to reverse hypoxia-mediated tumor resistance and overcome the restriction of PDT treatment.

Perfluoropolyether Nanoemulsion Encapsulating Chlorin e6 for Sonodynamic and Photodynamic Therapy of Hypoxic Tumor

“…It is noteworthy that the light irradiation power density (50 mW/cm 2 ) and irradiation dose (≤5.25 J/cm 2 ) in this study are a lot lower than those used on other oxygen-generating Ce6 nanoparticles, which relied on MnO 2 (150 mW/cm 2 , 90 J/cm 2 [ 72 ] or 100 mW/cm 2 , 30 J/cm 2 [ 56 ]) or H 2 O 2 (750 mW/cm 2 , 45 J/cm 2 [ 73 ]) decomposition to produce O 2 . This supports the applicability of our PFPE-based nanoformulation (i.e., Ce6-P/W NE) in delivering a large amount of O 2 to the hypoxic tumor site, consequently improving PDT efficiency.…”

Synthesis of iridium-based nanocomposite with catalase activity for cancer phototherapy

“…In addition, the amount of O 2 directly affects the efficiency of PDT [ 9 ]. Due to the rapid and uncontrolled proliferation of tumor cells, the O 2 levels in solid tumors are inadequate, thereby reducing the therapeutic efficiency of PDT [ 10 , 11 ]. Thus, researchers have proposed innovative strategies to enhance the O 2 concentration in tumors [ 12 ].…”

Application of nanotechnology for enhancing photodynamic therapy via ameliorating, neglecting, or exploiting tumor hypoxia

“…The hypoxic tumor cells are sensitized via PDT, and subsequently, the in vitro apoptosis of tumor cells is exacerbated. Other recent studies confirmed that the HIF-1 inhibition by acriflavine, 31 rapamycin, 32 and curcumin 33 could effectively sensitize PDT and radiotherapy. In another recent study by Liang and Wang et al, HIF-1 siRNA was loaded into a cationic porphyrin-grafted lipid microbubble.…”