Review Article A REVIEW OF NANOPARTICLE INNOVATIONS IN CANCER THERAPY: IMPLICATIONS, TARGETING MECHANISMS AND CLINICAL PROSPECTS LOKESHVAR R. , RAMAIYAN VELMURUGAN * Department of Pharmacology, Saveetha College of Pharmacy, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Saveetha Nagar, Chennai-602105, India * Corresponding author: Ramaiyan Velmurugan; * Email: velmuruganr.scop@saveetha.com Received: 26 Aug 2023, Revised and Accepted: 01 Mar 2024 ABSTRACT The main reason for morbidity and death globally is cancer, which has a complex pathophysiology. There are several traditional treatments for cancer, including chemotherapy, radiation therapy, targeted therapies, and immunotherapies. Multiple drug resistance, cytotoxicity, and lack of specificity pose significant challenges to cancer treatments. Molecular diagnostics and cancer treatment have been transformed by nanotechnology. For cancer treatment, nanoparticles (1–100 nm) are ideal because they are biocompatible, have low toxicity, excellent stability, high permeability, are precise and stable, and can deliver clear and accurate results. There are several main categories of nanoparticles. When it comes to the delivery of nanoparticle drugs, tumour characteristics and the tumour environment are considered. As well as providing advantages over conventional cancer treatments, nanoparticles prevent multidrug resistance, further overcoming their limitations. As new mechanisms are unravelled in studying multidrug resistance, nanoparticles are becoming more critical. Nano formulations have gained a new perspective on cancer treatment due to their many therapeutic applications. The number of approved nanodrugs has not increased significantly despite most research being conducted in vivo and in vitro. A review of nanoparticle oncological implications, targeting mechanisms, and approved nanotherapeutics is presented here. A current perspective on clinical translation is also provided, highlighting its advantages and challenges. Keywords: Cancer treatment, Pathophysiology, Nanoparticles, Nanotherapeutics © 2024 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2024v16i3.49358 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION The selections of articles for the current review were searched from specialized databases (Range of years: 1997-2021) such as Elsevier, PubMed, and Cambridge using the keywords cancer treatment, Pathophysiology, Nanoparticles, Nanotherapeutics. Other selections include articles from Springer, information from Internet sources, and online published articles from The Lancet Respiratory Medicine, Medscape, and Statpearls. World cancers have complex pathophysiology’s that contribute to death and morbidity. Chemotherapy, radiotherapy, targeted therapies, and immunotherapy are some of the traditional cancer treatments. There are several challenges associated with cancer treatments, including multiple drug resistance, cytotoxicity, and low specificity. The application of nanotechnology to cancer diagnostics and treatment has transformed both fields. The advantages of nanoparticles (1-100 nm) for cancer treatment include their biocompatibility, low toxicity, excellent stability, high permeability, precision and stability, and capacity to deliver precise and accurate results. Several main types of nanoparticles can be classified into [1, 2]. The tumour's characteristics and environment are considered for nanoparticle drug delivery. Nanoparticles have the advantage of overcoming the limitations of conventional cancer treatments, as well as preventing medical resistance to multiple drugs. Nanoparticles are also being studied as new mechanisms are unravelled in multidrug opposition. As a result of Nano formulations' many therapeutic applications, cancer treatment has taken on a whole new perspective. Despite most research being conducted in vitro and in vivo, the amount of approved Nano drugs hasn't increased significantly [3]. In this article, we discuss the oncological implications, targeting mechanisms, and approved applications of nanoparticles in oncology. In addition, the benefits and challenges of clinical translation are discussed. Cancer is a significant public health concern, which is the 2 nd leading reason for death globally. According to the American Cancer Society, 1.9 million new cancer cases will be in 2021. Surgery, chemotherapy, immunotherapy, radiation therapy, targeted therapy, and hormone therapy are common therapeutic approaches used in conventional cancer treatments [4, 5]. Cytostasis and cytotoxicity can be caused by chemotherapy and radiation [6], but the treatments have severe adverse effects and are often related to higher recurrence rates. There are also many other negative effects associated with this drug, including neuropathies, gastrointestinal disorders, hair loss, and fatigue. Cardio toxicity and pulmonary toxicity can also be caused by anthracyclines and bleomycin [7]. Precision therapy has become increasingly popular with the advent of targeted therapy [8]. Although they are still effective, drugs still have a large number of inherent adverse effects, including multi- drug resistance. Immunotherapeutic agents reduce recurrence rates, prevent distant metastases, and treat primary cancer [9]. As a result of immunotherapy, however, autoimmune diseases can develop. The effectiveness of immunotherapy against solid tumours is lower than that against lymphomas, according to several studies [10]. It is difficult for immune cells to penetrate the Extracellular Matrix (ECM) these cancers create [11]. These new targeted therapies and immunotherapies impair the epidermis and dermis' normal homeostatic functions by blocking key signalling pathways. Dermatologic Adverse Events (dAEs) result from this [12]. It has become increasingly important to find precise cancer treatments in recent years. Nanoparticles have recently been suggested to overcome the limitations of current therapeutic approaches. The disease affects the bone marrow, the digestive and skin systems, and the hair. There are also a few drug-specific adverse effects like cardio toxicity and pulmonary toxicity caused by anthracyclines and bleomycin. Precision therapy has grown as a result of targeted therapy [8]. While multiple-drug resistance has been found to limit therapeutic efficacy, there are still many inevitable adverse effects [7]. Immunotherapeutic agents have shown promise in treating primary cancers, preventing distant metastasis, and reducing recurrence rates [9]. Immunotherapy can, however, cause autoimmune diseases. The effectiveness of immunotherapy against solid tumours may differ from that against lymphomas [10]. A cancer cell-derived Extracellular Matrix (ECM) prevents immune cells from infiltrating the tissue [11]. Dermatologic Adverse Events (dAEs) can result from the development of immunotherapy and targeted therapy that interferes with signalling pathways important for malignant behaviour and maintenance of epidermal and dermal homeostasis [12]. As cancer treatments become more precise, new International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 16, Issue 3, 2024