Next Generation Calcium Nanomaterials: Disrupting Tumor Ca2⁺ Homeostasis for Enhanced Cancer Therapy

Lekshmi Gangadhar,1,* Siva Sankar Sana,2,* Raja Venkatesan,2,3 Richie R Bhandare,4,5 Seong-Cheol Kim,2 Haya Khader Ahmad Yasin4,5 1Department of Nanotechnology, Nanodot Research Private Limited, Nagercoil, Tamil Nadu, India; 2School of Chemical Engineering, Yeungnam University, Gyeongsan, Republic of Korea; 3Department of Biomaterials, Saveetha Dental College and Hospitals, SIMATS, Saveetha University, Chennai, Tamil Nadu, India; 4College of Pharmacy & Health Sciences, Ajman University, Ajman, United Arab Emirates; 5Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates*These authors contributed equally to this workCorrespondence: Seong-Cheol Kim, Email [email protected] Haya Khader Ahmad Yasin, Email [email protected]: Calcium-based nanotechnology is a rapidly growing field that leverages the unique properties of calcium compounds at the nanoscale to develop innovative materials and applications. This field centers around the manipulation and utilization of calcium compounds, such as calcium carbonate, calcium phosphate, and calcium oxide (CaO), when their dimensions are reduced to the nanoscale. Calcium compounds are generally biocompatible, biodegradable, cost-effective, and versatile, making them suitable for biomedical applications. Calcium homeostasis plays a critical role in cancer development and its progression. Understanding the mechanisms underlying cancer and calcium homeostasis disruption is crucial for developing effective strategies in cancer therapy. This review explores the therapeutic implications of intracellular calcium homeostasis, its crucial cancer development, and advances in therapy. The link between calcium homeostasis and tumor therapy is examined in this review, with particular attention paid to common calcium-based nanomaterials and their multifunctionality with other metals and compounds. Potential treatment options for disrupting calcium homeostasis include calcification therapy for tumor diagnosis, indirect prevention of tumor growth by altering the tumor microenvironment, and direct killing of tumor cells by inducing calcium overload. This review also examines the progress made in creating and using multifunctional calcium-based nanomaterials to treat cancer. Nanomaterials, which are categorized according to their main constituents (hydroxyapatite, carbonate, peroxide, and calcium phosphate), show great promise in ion interference, gene delivery, protein delivery, and drug delivery. Despite the challenges in this field, calcium-based nanotechnology holds immense potential for a wide range of applications, from healthcare to environmental remediation to energy. Continued research and development in this field will undoubtedly lead to more innovative and impactful technologies in the future.Keywords: calcium, homeostasis, cancer therapy, diagnosis, nanomedicine