| Hypoxia, a characteristic feature of tumors, is indispensable to tumor angiogenesis, metastasis, and multi drug resistance. Hypoxic avascular regions, deeply embedded inside the tumors significantly hinder delivery of therapeutic agents. The low oxygen tension results in resistance to the current applied anti-cancer therapeutics including radiotherapy, chemotherapy, and photodynamic therapy, the efficacy of which is firmly tied to the level of tumor oxygen supply. However, emerging data indicate that nanocarriers/nanodrugs can offer substantial benefits to improve the efficacy of current therapeutics, through modulation of tumor hypoxia. This review aims to introduce the most recent advances made in nanocarrier mediated targeting of tumor hypoxia. The first part is dedicated to the approaches by which nanocarriers could be designed to target/leverage hypoxia. These approaches include i) inhibiting Hypoxia Inducer Factor (HIF-1α); ii) hypoxia activated prodrugs/linkers; and iii) obligate anaerobe mediated targeting of tumor hypoxia. The second part, details novel nanosystems proposed to modulate tumor hypoxia through tumor oxygenation. These methods seek to lessen tumor hypoxia through vascular normalization, or reoxygenation therapy. The reoxygenation of tumor could be accomplished by: i) generation of oxygen filled nanocarriers; ii) natural/artificial oxygen nanocarriers; and iii) oxygen generators. The efficacy of each approach and their potential in cancer therapy is further discussed.presented the highest anti VEGF activity (0.0004 fold), whereas MCF-7 cells with the lowest hTERT inhibition (0.213) showed the lowest VEGF inhibition(0.0435) among the three studied cancer cells. We noticed that the modulation of VEGF-A and hTERT gene expression can be considered as a common target, accounting for the therapeutic potential of MOE on human breast, lung and prostate cancer cells. Conclusion: Altogether, it is suggested that the potent antiproliferative activity of the hydroalcoholic extract of Melissa officinalis is somehow explainable by its high potency to inhibit expression of the prominent oncogenes Bcl2, Her2,VEGF-A and hTERT in prostate cancer. In tumors with functional p53, including MCF-7 and A549 cancer cells, the role of p53, Bcl2 and Her2 is less significant. It appears that MOE exerts its antiproliferative effects in these cancer cells partly via concurrent downregulation of VEGF-A and hTERT. Additional studies are needed to clarify the role of other active molecules in cancer
cells harboring functional p53. |