Nanoparticles for immobilization and delivery of temozolomide: Functional design of carriers, advances, limitations and opportunities for glioblastoma co-therapy

Glioblastoma remains one of the most lethal forms of cancer due to its infiltrative growth mechanism, intrinsic and acquired drug resistance. Traditional tumor resection combined with radiotherapy and chemotherapy with temozolomide does not allow us to achieve stable remission, and innovative approaches to treatment are limited to modestly increasing the median survival of patients. Hence, glioblastoma therapy is a challenge and a platform for continuous improvement of nanomedicine methods. Therefore, this review considers the aspects of obtaining and functionalising of nanoparticle carriers in the context with recent advances in nanomedicine, ascertainment of molecular mechanisms in temozolomide antitumor activity, the emergence and overcoming of drug resistance to it. The main approaches to obtaining multifunctional nanoparticles with an inorganic and organic core in order to provide combined and targeted glioblastoma therapy with temozolomide using as an antitumor drug are shown. With an emphasis on nanomaterials science, a systematic analysis of temozolomide immobilization methods by nanosized carriers, as well as other pharmacologically active and auxiliary substances that contribute to increasing the effectiveness of glioblastoma therapy. The main achievements and limitations of the temozolomide-containing nanosized systems for the glioblastoma treatment are outlined, as well as the main development prospects for this area of nanomedicine. A decisive success in the field of glioblastoma chemotherapy requires further development of methods for targeting delivery and reducing the immunogenicity of nanoparticles and a breakthrough in understanding the mechanisms and searching for methods for suppressing acquired drug resistance of tumor cells.