TY - JOUR
T1 - The role of autophagy at the nano/bio interface - underlying mechanisms and therapeutic potential in cancer
AU - You, Liwei
AU - Feng, Zhenhan
AU - Zhao, Yuliang
AU - Meng, Huan
AU - Zhu, Motao
N1 - Funding Information:
in tumor development, cell-type-specific nano-formulations for targeted therapy are needed to manipulate autophagy in cancer cells, cancer-associated macrophages APCs, or other cells within TME. For example, to deliver cancer antigens for cancer immunotherapy, autophagy inducers could be co-delivered by nanoparticles to promote autophagy-dependent antigen-presentation for a potent antitumor immune response. By contrast, autophagy inhibitors could be delivered specifically to cancer cells by nanoparticles to prohibit tumor nutrition supply when aiming at cancer metabolism. In addition, with the advent of nanotechnology, it has become popular to consider constructing co-delivery nanocarriers or designing nano-enabled combination therapy to implement “autophagy interference” + “X”. The candidates for “X” could be a nuclear acid-based active pharmaceutical ingredient (API) or their combinations, which per se largely require nano-formulation. The apparent advantage of such an approach is the “synergy” by implementing synchronized PKs, multi-target combinations, and improved safety profile of the combination. These become the major strengths to augment the likelihood of a successful tumor therapy in vivo. The third interesting aspect is to systemically dissect the critical roles of nanomaterial properties in autophagy regulation. However, when attempting to do this, one should closely monitor the extent of autophagy alternation to avoid unexpected toxic responses due to engineered nanomaterials' diverse physical and chemical properties. This may become the basis of designing drug-free nano-formulations to replace the classical pharmacological compounds that target autophagy. Acknowledgements H. Meng and M. Zhu thank the startup funding support from National Center for Nanoscience and Technology, CAS (E1763911, E1773911). Y. Zhao thanks the support from Strategic Priority Research Program of Chinese Academy of Sciences (Grant No. XDB36000000). Conflict of interest The authors declare no conflicts of interest. For signed statements, please contact the journal office: [email protected] Quote this article as You L, Feng Z, Zhao YL, Meng H, Zhu, M, The Role of Autophagy at the Nano/Bio Interface - Underlying Mechanisms and Therapeutic Potential in Cancer, Precis. Nanomed. 2020;4(3):821-839, https://doi.org/10.33218/001c.28984
Publisher Copyright:
© 2021, Andover House, Inc.. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Autophagy plays an essential role in maintaining cellular homeostasis by responding to certain stressed conditions such as nutrient deprivation, organelle damage, pathogen infection, and exposure to certain nanomaterials. Through deliberate tuning of the physicochemical properties, the fate of nanomaterial-treated cells is subjected to various cellular toxicity, stress responses, and immune responses, some of which involve various autophagic mechanisms. Beginning from the molecular basis of the autophagy machinery, we briefly introduce the major understanding of autophagy in inflammation, immunity, cancer metabolism, and therapy. Different working mechanisms will be discussed to classify the impact of physicochemical characteristics on autophagy induction or inhibition by engineered nanomaterials. From the perspective of autophagy-targeting cancer therapeutics, we will further delineate the advanced nano-formulations for improved drug delivery to impact autophagy in the setting of cancer diseases and designing co-delivery nanomedicine that targets autophagy along with another major cancer pathway to achieve in vivo synergy. Moreover, cancer immunotherapy, aiming at immune cells or checkpoints, is also integrated with autophagy-regulatory components using multiple nano-platforms as an emerging strategy for cancer treatment. Considering the recent breakthroughs of nanotechnology targeting autophagy in cancer cells, antigen-presenting cells, or other cell types within tumor microenvironment by precisely designed nanomedicine may provide additional solutions for cancer treatment through autophagy-dependent metabolic regulation or immune pathways. However, one should closely monitor the extent of autophagy alternation and side effects from certain nanoparticles to avoid severe toxic responses.
AB - Autophagy plays an essential role in maintaining cellular homeostasis by responding to certain stressed conditions such as nutrient deprivation, organelle damage, pathogen infection, and exposure to certain nanomaterials. Through deliberate tuning of the physicochemical properties, the fate of nanomaterial-treated cells is subjected to various cellular toxicity, stress responses, and immune responses, some of which involve various autophagic mechanisms. Beginning from the molecular basis of the autophagy machinery, we briefly introduce the major understanding of autophagy in inflammation, immunity, cancer metabolism, and therapy. Different working mechanisms will be discussed to classify the impact of physicochemical characteristics on autophagy induction or inhibition by engineered nanomaterials. From the perspective of autophagy-targeting cancer therapeutics, we will further delineate the advanced nano-formulations for improved drug delivery to impact autophagy in the setting of cancer diseases and designing co-delivery nanomedicine that targets autophagy along with another major cancer pathway to achieve in vivo synergy. Moreover, cancer immunotherapy, aiming at immune cells or checkpoints, is also integrated with autophagy-regulatory components using multiple nano-platforms as an emerging strategy for cancer treatment. Considering the recent breakthroughs of nanotechnology targeting autophagy in cancer cells, antigen-presenting cells, or other cell types within tumor microenvironment by precisely designed nanomedicine may provide additional solutions for cancer treatment through autophagy-dependent metabolic regulation or immune pathways. However, one should closely monitor the extent of autophagy alternation and side effects from certain nanoparticles to avoid severe toxic responses.
KW - Autophagy
KW - Cancer therapy
KW - Engineered nanomaterials
KW - Immune response
KW - Nanomedicine
UR - http://www.scopus.com/inward/record.url?scp=85162075023&partnerID=8YFLogxK
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U2 - 10.33218/001c.28984
DO - 10.33218/001c.28984
M3 - Review article
AN - SCOPUS:85162075023
SN - 2639-9431
VL - 4
SP - 821
EP - 839
JO - Precision Nanomedicine
JF - Precision Nanomedicine
IS - 3
ER -