Hypoxia-responsive nanomedicine to overcome tumor microenvironment-mediated resistance to chemo-photodynamic therapy

H. Lee; D. K. Dey; K. Kim; S. Kim; E. Kim; S. C. Kang; V. K. Bajpai; Y. S. Huh

doi:10.1016/j.mtadv.2022.100218

Hypoxia-responsive nanomedicine to overcome tumor microenvironment-mediated resistance to chemo-photodynamic therapy

H. Lee, D. K. Dey, K. Kim, S. Kim, E. Kim, S. C. Kang, V. K. Bajpai, Y. S. Huh

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Hypoxia is a feature of solid tumors that greatly hinders cancer treatment. Here, we developed hypoxia-responsive nanoparticles (NPs) that selectively release chlorin e6 (Ce6) and paclitaxel (PTX) under hypoxic conditions. To prepare the hypoxia-responsive NPs, PTX-loaded HSA NPs (PHNPs) were functionalized with 4,4′-azodianiline (Azo) as a linker for the PHNPs and Ce6 (CA/PHNPs). The CA/PHNPs were then functionalized with RGD-conjugated poly(ethylene glycol) (RP/CA/PHNPs). The azo group (-N[dbnd]N-) present in Azo was reductively cleaved under hypoxic conditions to release Ce6 and PTX. The release of Ce6 due to azo cleavage under hypoxia resulted in a uniform distribution of Ce6 within HeLa cells and spheroids, enhancing antitumor activity even in a hypoxic environment. The RP/CA/PHNPs also showed excellent antitumor effects in a HeLa cell xenograft mouse model. Thus, this strategy for controlling the drug distribution within a hypoxic tumor microenvironment (TME) potentially represents a very effective strategy for the removal of solid tumors with a hypoxic TME by improving the efficiency of photodynamic therapy and chemotherapy.

Original language	English
Article number	100218
Journal	Materials Today Advances
Volume	14
DOIs	https://doi.org/10.1016/j.mtadv.2022.100218
State	Published - Jun 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Keywords

Drug delivery system
Hypoxia
In vivo xenograft model
Photodynamic therapy
Spheroid
Tumor microenvironment (TME)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.mtadv.2022.100218

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title = "Hypoxia-responsive nanomedicine to overcome tumor microenvironment-mediated resistance to chemo-photodynamic therapy",

abstract = "Hypoxia is a feature of solid tumors that greatly hinders cancer treatment. Here, we developed hypoxia-responsive nanoparticles (NPs) that selectively release chlorin e6 (Ce6) and paclitaxel (PTX) under hypoxic conditions. To prepare the hypoxia-responsive NPs, PTX-loaded HSA NPs (PHNPs) were functionalized with 4,4′-azodianiline (Azo) as a linker for the PHNPs and Ce6 (CA/PHNPs). The CA/PHNPs were then functionalized with RGD-conjugated poly(ethylene glycol) (RP/CA/PHNPs). The azo group (-N[dbnd]N-) present in Azo was reductively cleaved under hypoxic conditions to release Ce6 and PTX. The release of Ce6 due to azo cleavage under hypoxia resulted in a uniform distribution of Ce6 within HeLa cells and spheroids, enhancing antitumor activity even in a hypoxic environment. The RP/CA/PHNPs also showed excellent antitumor effects in a HeLa cell xenograft mouse model. Thus, this strategy for controlling the drug distribution within a hypoxic tumor microenvironment (TME) potentially represents a very effective strategy for the removal of solid tumors with a hypoxic TME by improving the efficiency of photodynamic therapy and chemotherapy.",

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author = "H. Lee and Dey, {D. K.} and K. Kim and S. Kim and E. Kim and Kang, {S. C.} and Bajpai, {V. K.} and Huh, {Y. S.}",

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year = "2022",

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doi = "10.1016/j.mtadv.2022.100218",

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AU - Lee, H.

AU - Dey, D. K.

AU - Kim, K.

AU - Kim, S.

AU - Kim, E.

AU - Kang, S. C.

AU - Bajpai, V. K.

AU - Huh, Y. S.

PY - 2022/6

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AB - Hypoxia is a feature of solid tumors that greatly hinders cancer treatment. Here, we developed hypoxia-responsive nanoparticles (NPs) that selectively release chlorin e6 (Ce6) and paclitaxel (PTX) under hypoxic conditions. To prepare the hypoxia-responsive NPs, PTX-loaded HSA NPs (PHNPs) were functionalized with 4,4′-azodianiline (Azo) as a linker for the PHNPs and Ce6 (CA/PHNPs). The CA/PHNPs were then functionalized with RGD-conjugated poly(ethylene glycol) (RP/CA/PHNPs). The azo group (-N[dbnd]N-) present in Azo was reductively cleaved under hypoxic conditions to release Ce6 and PTX. The release of Ce6 due to azo cleavage under hypoxia resulted in a uniform distribution of Ce6 within HeLa cells and spheroids, enhancing antitumor activity even in a hypoxic environment. The RP/CA/PHNPs also showed excellent antitumor effects in a HeLa cell xenograft mouse model. Thus, this strategy for controlling the drug distribution within a hypoxic tumor microenvironment (TME) potentially represents a very effective strategy for the removal of solid tumors with a hypoxic TME by improving the efficiency of photodynamic therapy and chemotherapy.

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KW - Hypoxia

KW - In vivo xenograft model

KW - Photodynamic therapy

KW - Spheroid

KW - Tumor microenvironment (TME)

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Hypoxia-responsive nanomedicine to overcome tumor microenvironment-mediated resistance to chemo-photodynamic therapy

Abstract

Bibliographical note

Keywords

UN SDGs

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