Cancer remains a major threat to human health worldwide. suggesting the target-tailoring ability of nanomedicine. strong class=”kwd-title” Keywords: metallofullerenol, Gd@C82(OH)22, encaging tumor, drug design, key and lock principle 1. Introduction According to the latest cancer statistics issued by the American Cancer Society in 2019, the death rate Namitecan from all cancers combined has declined Namitecan by 27% since 1991 owing to increased awareness, decreased IL12RB2 smoking and progression made in early detection and treatment . However, cancer, as a leading cause of morbidity and mortality, still remains a major threat to human health worldwide . In the USA, 1,762,450 new cancer cases have been reported in 2019 and 606,880 deaths are projected to occur in 2019 . Globally, an alarming increase in the incidence of all-cancer cases has been estimated from 12.7 million new cases in 2008 to 22.2 million by 2030 . The large threat of cancer to human health has posed a great challenge for medical practice in cancer diagnosis and treatment. Currently, three principle strategies available to treat cancers are still confined to surgery, chemotherapy and radiotherapy . Either mechanical removal of tumors by surgery or direct destruction of malignant cells by poisoning or irradiating inevitably induces unsatisfactory outcomes. Chemotherapy, dependent on the cytotoxic effects of chemotherapeutics, has witnessed high occurrences of severe side effects due to its unselective damage both to tumor and normal tissues . In some cases, patients suffer so much that chemotherapy is Namitecan forced to be terminated. More importantly, multidrug resistance is another challenge confronted by chemotherapy, which significantly limits the effectiveness of chemotherapy and impedes the progress of patient prognosis [6,7]. Approximately, 90% of deaths from ovarian cancer could be attributed to multidrug resistance . Despite the emergence of molecular-targeted chemotherapy with enhanced selectivity in late decades, adverse reactions are still unavoidable which, at least partially, is attributed to the diversity and complexity of target biomolecules [9,10]. Therefore, a new anti-cancer strategy is in great need to reduce or even avoid the risks of severe toxicity resulting from the traditional chemotherapy. Encouragingly, the recent rapidly-developing nanotechnology offers great opportunities to improve the antineoplastic efficiency and simultaneously smooth away the drawbacks of traditional chemotherapy . Globally, intensive research on the development of clinic-aimed nanotechnology has attracted increasing attention as an emerging hotspot of the nanoscience field. Nationally, facing the global competitions, our government has urgently encouraged the acceleration of the development of nanotechnology with substantial support and investment for the transition of the laboratory innovation to the practice, especially those promising breakthroughs in clinical applications . The unique physicochemical properties of nanomaterials attractive for clinical applications, have prompted the development of nanomedicine and these properties also influence the behaviors of nanomedicine in the body [13,14]. The authors previously discussed the impacts of nanomaterials properties (size, shape, surface, et Namitecan al.) on the metabolism of nanomaterials including circulation, organ-specific extravasation and clearance in vivo, which highlighted the flexible and controllable manipulation of the nanomaterials behaviors by modulating their physicochemical properties . Moreover, nano-scaled size endows nanomaterials with large surface areas and surface-hyperactivity, favorable for drug vectors. In the field of cancer nanomedicine research, biocompatible nanoparticles, such as liposomes and biodegradable polymers, can be loaded with conventional chemotherapeutic drugs, especially those with low solubility, to achieve a controlled drug release profile . Nanovectors facilitate the biodistribution of drugs and improve the bioavailability. The encapsulation efficiency of nanoparticles can be optimized by controllable components and formulation parameters [17,18]. Due to their small sizes, these nanovectors carrying anti-cancer drugs could penetrate into the tissue and passively target tumor tissues by the enhanced permeability and retention (ERP) effect . Recently, great progress has been made in the blood-brain barrier-crossing nanotechnology,.