Enhanced porphyrin-based fluorescence imaging-guided photodynamic/photothermal synergistic cancer therapy by mitochondrial targeting

Abstract

Mitochondria are the power plants of the cell and play key roles in activating the apoptotic pathway in cancer cells, which are readily susceptible to cytotoxic reactive oxygen species and temperature elevations. Herein, we develop a "nanomissile" that targets mitochondria to enhance tumor treatment effects by facilitating mitochondrial dysfunction and releasing cytochrome C to activate the apoptotic pathway of cancer cells under 650-nm laser irradiation. Porphyringrafted polydopamine nanomaterial (PTPF-MitP) is designed as a nanomissile, with integrated O 2 -evolving photodynamic therapy and moderate photothermal therapy, which can selectively deliver to the mitochondria through a targeting unit, MitP. The cytotoxicity of PTPF-MitP to human lung tumor cells is twice as high as that of PTPF that does not have mitochondrial targeting units. In addition, it represents a realtime visualization and highly efficient treatment for tumor sites in vivo. This development represents a viable strategy for cancer therapy.

Innovative strategies for photodynamic therapy against hypoxic tumor

“…Lu et al. developed a mitochondria-targeted nanoplatfrom (PTPF-MitP) [136] , which possessed an excellent performance in activating the apoptosis pathway in cancer treatment under hypoxic TME through the release of apoptotic factor cytochrome C. Moreover, PTPF-MitP also had the ability to trigger H 2 O 2 decomposition serving as a nanoenzyme, thus further tackling the issue of hypoxia-induced PDT limitation. Cell viability was observed to significantly decrease in groups treated with PTPF-MitP compared with the PTPF group, implying the high cytotoxicity of MitP served as a mitochondrial targeting unit.…”

Nanomaterials for photothermal cancer therapy

“…37 Porphyrin-based nanomaterials are a class of organic photothermal conversion materials that have attracted signicant attention for their potential applications in PTT. 38 One of the key features of porphyrin-based nanomaterials is their strong light absorption properties in the visible and nearinfrared regions, which makes them suitable for using in PTT. 16,24,39 Zhou et al developed two-dimensional gold-porphyrinbased nanosheets, Au0-Por, with outstanding photothermal properties and high drug loading capability by mixing tetrachloroaurate and meso-tetra(pyridyl)porphyrin (TPyP) solutions and reducing gold ions.…”

“…37 Porphyrin-based nanomaterials are a class of organic photothermal conversion materials that have attracted significant attention for their potential applications in PTT. 38 One of the key features of porphyrin-based nanomaterials is their strong light absorption properties in the visible and near-infrared regions, which makes them suitable for using in PTT. 16,24,39…”

A biocompatible pure organic porous nanocage for enhanced photodynamic therapy

“…[20][21][22][23] Several strategies have been applied to fight against the aggregation-caused-quenching (ACQ) effect, including modification of long amphiphilic chains, introduction of molecular spacers, and loading porphyrin PSs at nanoparticle surfaces, but with limited success. [24][25][26][27] The development of porous frameworks provides a new solution to weaken the p-p stacking of porphyrin-based PSs. 28,29 One of the particular examples is metal-organic frameworks (MOFs) where the high porosity of MOFs can spatially separate these porphyrin molecules to avoid close p-p stacking and weaken the ACQ effect.…”

“…20–23 Several strategies have been applied to fight against the aggregation-caused-quenching (ACQ) effect, including modification of long amphiphilic chains, introduction of molecular spacers, and loading porphyrin PSs at nanoparticle surfaces, but with limited success. 24–27…”