The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway plays a crucial role in the regulation of autophagy, a cellular mechanism vital for homeostasis through the degradation of damaged organelles and proteins. The dysregulation of this pathway is significantly associated with cancer progression, metastasis, and resistance to therapy. Targeting the PI3K/AKT/mTOR signaling pathway presents a promising strategy for cancer treatment; however, traditional therapeutics frequently encounter issues related to nonspecific distribution and systemic toxicity. Nanoparticle-based drug delivery systems represent a significant advancement in addressing these limitations. Nanoparticles enhance the bioavailability, stability, and targeted delivery of therapeutic agents, facilitating the precise modulation of autophagy in cancer cells. Functionalized nanoparticles, such as liposomes, polymeric nanoparticles, and metal-based nanocarriers, facilitate targeted drug delivery to tumor tissues, minimizing off-target effects and improving therapeutic efficacy. These systems can deliver multiple agents concurrently, enhancing the modulation of PI3K/AKT/mTOR-mediated autophagy and related oncogenic pathways. This review examines advancements in nanoparticle-mediated drug delivery that target the PI3K/AKT/mTOR pathway, emphasizing their contribution to improving precision and minimizing side effects in cancer therapy. The integration of nanotechnology with molecularly targeted therapies presents substantial potential for addressing drug resistance. Future initiatives must prioritize the optimization of these systems to enhance clinical translation and patient outcomes.

Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of female reproductive health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, and infertility. Existing research emphasizes the crucial significance of autophagy in embryo implantation, specifically in the endometrium, highlighting its necessity in ensuring proper fetal development. Although some knowledge has been gained, there is still a lack of research on the specific molecular impacts of autophagy on the quality of oocytes, the growth of follicles, and general reproductive health. Autophagy plays a role in the maturation, quality, and development of oocytes. It is also involved in reproductive aging, contributing to reductions in reproductive function that occur with age. This review explores the physiological functions of autophagy in the female reproductive system, its participation in reproductive toxicity, and its important connections with the endometrium and embryo. In addition, this study investigates the possibility of emerging treatment approaches that aim to modify autophagy, using both natural substances and synthetic molecules, to improve female fertility and reproductive outcomes. Additionally, this review intends to inspire future exploration into the intricate role of autophagy in female reproductive health by reviewing recent studies and pinpointing areas where current knowledge is lacking. Subsequent investigations should prioritize the conversion of these discoveries into practical uses in the medical field, which could potentially result in groundbreaking therapies for infertility and other difficulties related to reproduction. Therefore, gaining a comprehensive understanding of the many effects of autophagy on female fertility would not only further the field of reproductive biology but also open new possibilities for diagnostic and treatment methods.

Hypoxia-Inducible Factor-1α (HIF-1α) is crucial in the progression of ovarian cancer, especially in influencing its tumor microenvironment and promoting pathogenic pathways that worsen female infertility. In hypoxic settings, HIF-1α is stabilized and activates the transcription of genes associated with angiogenesis, metabolic reprogramming, epithelial-to-mesenchymal transition, and therapeutic resistance. Angiogenesis and glycolytic reprogramming mediated by HIF-1 tumor proliferation, survival, and metastasis. Its dysfunction concurrently impairs ovarian homeostasis, undermining follicular growth, hormone synthesis, and the ovarian vascular network, consequently contributing to infertility. Moreover, HIF-1α induces persistent inflammation and oxidative stress, promoting an environment damaging to reproductive health. Due to its dual function in ovarian cancer growth and infertility, HIF-1α is a potential therapeutic target. Strategies including small molecule inhibitors and nanoparticle-mediated delivery of drugs possess the potential to reduce HIF-1α activity, hence reducing cancer progression while protecting fertility. This review seeks to clarify the molecular basis of HIF-1α in ovarian cancer and its effects on female infertility, providing insights into novel treatment approaches that target both controlling the disease and preserving fertility.

Autophagy, an intrinsic catabolic mechanism that eliminates misfolded proteins, dysfunctional organelles, and lipid droplets, plays a vital function in energy balance and cytoplasmic quality control, in addition to maintaining cellular homeostasis. Liver cancer such as hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths globally and shows resistance to several anticancer drugs. Despite the rising incidence and poor prognosis of malignant HCC, the underlying molecular mechanisms driving this aggressive cancer remain unclear. Several natural compounds, such as phytochemicals of dietary and non-dietary origin, affect hepatocarcinogenesis signaling pathways in vitro and in vivo, which may help prevent and treat HCC cells. Current HCC cells treatments include chemotherapy, radiation, and surgery. However, these standard therapies have substantial side effects, and combination therapy enhances side effects for an acceptable therapeutic benefit. Therefore, there is a need to develop treatment strategies for HCC cells that are more efficacious and have fewer adverse effects. Multiple genetic and epigenetic factors are responsible for the HCC cells to become resistant to standard treatment. Autophagy contributes to maintain cellular homeostasis, which activates autophagy for biosynthesis and mitochondrial regulation and recycling. Therefore, modifying autophagic signaling would present a promising opportunity to identify novel therapies to treat HCC cells resistant to current standard treatments. This comprehensive review illustrates how natural compounds demonstrate their anti-hepatocellular carcinoma function through autophagy.

Cancer remains a leading cause of death worldwide, necessitating new treatment strategies. Bioactive natural products are a promising source of anticancer drugs because of their complex structures and ability to target multiple pathways, such as inducing apoptosis and inhibiting angiogenesis. However, issues like poor solubility, stability, and bioavailability have limited their clinical use. Nanoparticle-based drug delivery offers a revolutionary approach by improving the pharmacokinetics and targeted delivery of anticancer agents, including natural compounds. Different types of nanoparticles, such as liposomes, polymeric nanoparticles, and metallic nanoparticles, use the enhanced permeability and retention (EPR) effect to increase drug accumulation in tumors while reducing off-target toxicity. This study explores the potential of combining natural products with nanoparticle delivery systems to overcome drug resistance and enhance therapeutic effectiveness. It highlights significant achievements, including FDA-approved nanoparticle-based drugs and innovative combination therapies. The review also discusses current limitations, such as toxicity, scalability, and regulatory hurdles, while looking ahead to emerging themes like smart nanoparticles and personalized medicine. Ultimately, this review emphasizes the importance of integrating bioactive natural products with nanotechnology, presents future research directions, and advocates for translational studies and clinical trials to advance cancer treatment.

Autophagy is a globally conserved cellular activity that plays a critical role in maintaining cellular homeostasis through the breakdown and recycling of cellular constituents. In recent years, there has been much emphasis given to its complex role in cancer stem cells (CSCs) and stem cell treatment. This study examines the molecular processes that support autophagy and how it is regulated in the context of CSCs and stem cell treatment. Although autophagy plays a dual role in the management of CSCs, affecting their removal as well as their maintenance, the intricate interaction between the several signaling channels that control cellular survival and death as part of the molecular mechanism of autophagy has not been well elucidated. Given that CSCs have a role in the development, progression, and resistance to treatment of tumors, it is imperative to comprehend their biological activities. CSCs are important for cancer biology because they also show a tissue regeneration model that helps with organoid regeneration. In other words, the manipulation of autophagy is a viable therapeutic approach in the treatment of cancer and stem cell therapy. Both synthetic and natural substances that target autophagy pathways have demonstrated promise in improving stem cell-based therapies and eliminating CSCs. Nevertheless, there are difficulties associated with the limitations of autophagy in CSC regulation, including resistance mechanisms and off-target effects. Thus, the regulation of autophagy offers a versatile strategy for focusing on CSCs and enhancing the results of stem cell therapy. Therefore, understanding the complex interactions between autophagy and CSC biology would be essential for creating therapeutic treatments that work in both regenerative medicine and cancer treatment.