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Increasing research emphasizes subcellular organelle targeting, especially mitochondria, which regulate tumor initiation, progression, and apoptosis. 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\nNano-Drug Delivery Systems for Cancer Therapy  \nLi Huang 1 , *, Yujing Lei 2 , *, Piao Zheng 3 , Qingshan Chen4 , Chenyang Wang 1 , Jie Ma 5  \n1Pharmaceutical Preparation Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2College of Medicine and Medical Technology, Changsha Cultural Creative and Arts Vocational College, Changsha, People’s Republic of China; 3Department of Discipline Development and Research Management, The Second Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 4The Department of Hepatobiliary Pancreatic Hernia Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 5Department of Traditional Chinese Medicine, Hunan Institute for Drug Control, Changsha, People’s Republic of China  \n*These authors contributed equally to this work  \nCorrespondence: Li Huang, Email [huanglily0101@hnucm.edu.cn](huanglily0101@hnucm.edu.cn)  \n\n| Abstract: Cancer remains a major disease that poses a serious threat to human health. Conventional treatments such as radiotherapy, chemotherapy, and surgery are limited by systemic toxicity and tumor recurrence, which hinder the achievement of highly efficient and specific therapy. The development of nanodrug delivery systems has provided new opportunities for cancer treatment. Utilizing mechanisms such as passive targeting (eg, the EPR effect) and active targeting (eg, peptide-based surface modification), these systems can precisely deliver drugs to tumor sites, thereby significantly reducing systemic toxicity. In recent years, research focus has shifted from tissue-level targeting to subcellular organelle targeting, particularly of mitochondria. Functioning as cellular power plants, mitochondria are deeply involved in tumor initiation, progression, and the regulation of apoptosis, making them important targets for cancer therapy. Based on the structural features of mitochondria and their dysfunctional role in cancer, this review systematically explores strategies for mitochondriatargeted nanodrug delivery and summarizes the latest research advances along with future directions in cancer treatment. A unique aspect of this review is its systematic integration of the design principles from mitochondrial substructure characteristics to multi-level targeting strategies, underscoring the innovative potential of nanocarriers in overcoming tumor drug resistance and enabling precise intervention. This work thereby provides a theoretical basis and novel insights for precision oncology.\u003Cbr>Keywords: nano-drug delivery carriers, mitochondrial targeting, tumor microenvironment, responsive nanocarriers |\n| --- |\n| Introduction\u003Cbr>As a significant threat to human health, cancer has long been a central focus and major challenge in medical research. According to the “Global Cancer Statistics 2022” published by the International Agency for Research on Cancer (IARC) of the World Health Organization, there were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer. With demographics-based predictions indicating that the number of new cases of cancer will reach 35 million by 2050.1 Conventional therapeutic modalities, including radiotherapy, chemotherapy, and surgery, are often compromised by dose-limiting systemic toxicity, drug resistance,2 and the risk of tumor recurrence.3 Therefore, there is an urgent need to develop treatment strategies that must not only target tumor cells precisely but also minimize damage to healthy cells.\u003Cbr>Mitochondria, often termed the “powerhouse” of the cell, play a central role in tumor initiation and progression. They not only generate adenosine triphosphate (ATP) through oxidative phosphorylation, supplying the energy requir","cbCaimMAeEKjnHW3","https://ap.wps.com/l/cbCaimMAeEKjnHW3","pdf",2764757,23,"English","# Introduction\n# Mitochondria in Cancer Biology\n# Mitochondria-Targeted Nano-Drug Delivery Strategies\n# Future Directions in Mitochondria-Targeted Therapy","[{\"question\":\"Why do conventional cancer treatments still face major limitations?\",\"answer\":\"Radiotherapy, chemotherapy, and surgery are often limited by systemic toxicity, emerging drug resistance, and the risk of tumor recurrence.\"},{\"question\":\"What makes mitochondria a key target for cancer therapy?\",\"answer\":\"Mitochondria drive tumor initiation and progression, influence metabolic reprogramming, and regulate apoptosis, so their dysfunction is closely tied to malignant behavior.\"},{\"question\":\"How do mitochondria-targeted nanodrug delivery systems improve treatment precision?\",\"answer\":\"They use passive and active targeting strategies to deliver drugs specifically to tumor sites and, more recently, aim to overcome challenges related to entering mitochondrial structures and resisting tumor mechanisms.\"}]","Recent Advances in Mitochondria-Targeted Nano-Drug Delivery Systems for Cancer Therapy - Review Article | PDF",1790149037,58]