Nanoliposomes for doxorubicin delivery: Reversing drug resistance, stimuli-responsive carriers and clinical translation

© 2022 Elsevier B.V.Cancer is still a major threat to human life that is characterized by abnormal proliferation and metastasis of cancer cells. Chemotherapy is procedure of using anti-cancer drugs for preventing dissemination and proliferation of tumor cells to kill them in improving survival rate and prognosis of patients. Chemotherapy has been a common conventional therapy for cancer, and it can be used along with surgical resection in cancer patients. However, drug resistance has led to chemotherapy failure in patients, especially in advanced and metastatic stages. Therefore, nano-scale delivery systems have been developed for reversing drug resistance and potentiating efficacy of chemotherapy agents. Liposomes are spherical vesicles with low particle size and high biocompatibility that have been used for drug delivery in cancer suppression. Liposomes can increase internalization of doxorubicin (DOX) as an anti-cancer drug in tumor cells to boost its cytotoxicity. Furthermore, co-delivery of DOX with other anti-tumor drugs or gene therapy can lead to synergistic cancer therapy. pH-, redox-, light- and multi-sensitive liposomes have been designed for precise delivery of DOX in cancer suppression. Modification of liposomes with ligands such as hyaluronic acid that binds to CD44 receptor, enhances selectivity towards cancer cells. Furthermore, DOX-loaded liposomes mainly internalize in cancer cells via endocytosis that is dependent on different factors such as particle size, zeta potential and other physico-chemical properties

Progress in targeting PTEN/PI3K/Akt axis in glioblastoma therapy: Revisiting molecular interactions

Glioblastoma (GBM) is one of the most malignant cancers of central nervous system and due to its sensitive location, surgical resection has high risk and therefore, chemotherapy and radiotherapy are utilized for its treatment. However, chemoresistance and radio-resistance are other problems in GBM treatment. Hence, new therapies based on genes are recommended for treatment of GBM. PTEN is a tumor-suppressor operator in cancer that inhibits PI3K/Akt/mTOR axis in diminishing growth, metastasis and drug resistance. In the current review, the function of PTEN/PI3K/Akt axis in GBM progression is evaluated. Mutation or depletion of PTEN leads to increase in GBM progression. Low expression level of PTEN mediates poor prognosis in GBM and by increasing proliferation and invasion, promotes malignancy of tumor cells. Moreover, loss of PTEN signaling can result in therapy resistance in GBM. Activation of PTEN signaling impairs GBM metabolism via glycolysis inhibition. In contrast to PTEN, PI3K/Akt signaling has oncogenic function and during tumor progression, expression level of PI3K/Akt enhances. PI3K/Akt signaling shows positive association with oncogenic pathways and its expression similar to PTEN signaling, is regulated by non-coding RNAs. PTEN upregulation and PI3K/Akt signaling inhibition by anti-cancer agents can be beneficial in interfering GBM progression. This review emphasizes on the signaling networks related to PTEN/PI3K/Akt and provides new insights for targeting this axis in effective GBM treatment