Oncolytic virus delivery: from nano-pharmacodynamics to enhanced oncolytic effect
نویسندگان
چکیده
With the advancement of a growing number of oncolytic viruses (OVs) to clinical development, drug delivery is becoming an important barrier to overcome for optimal therapeutic benefits. Host immunity, tumor microenvironment and abnormal vascularity contribute to inefficient vector delivery. A number of novel approaches for enhanced OV delivery are under evaluation, including use of nanoparticles, immunomodulatory agents and complex viral-particle ligands along with manipulations of the tumor microenvironment. This field of OV delivery has quickly evolved to bioengineering of complex nanoparticles that could be deposited within the tumor using minimal invasive image-guided delivery. Some of the strategies include ultrasound (US)-mediated cavitation-enhanced extravasation, magnetic viral complexes delivery, image-guided infusions with focused US and targeting photodynamic virotherapy. In addition, strategies that modulate tumor microenvironment to decrease extracellular matrix deposition and increase viral propagation are being used to improve tumor penetration by OVs. Some involve modification of the viral genome to enhance their tumoral penetration potential. Here, we highlight the barriers to oncolytic viral delivery, and discuss the challenges to improving it and the perspectives of establishing new modes of active delivery to achieve enhanced oncolytic effects.
منابع مشابه
Developing oncolytic Herpes simplex virus type 1 through UL39 knockout by CRISPR-Cas9
Objective(s): Oncolytic Herpes simplex virus type 1 (HSV-1) has emerged as a promising strategy for cancer therapy. However, development of novel oncolytic mutants has remained a major challenge owing to low efficiency of conventional genome editing methods. Recently, CRISPR-Cas9 has revolutionized genome editing.Materials and Methods: I...
متن کاملSilk-elastin-like protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus.
BACKGROUND Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. METHODS Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. RESULTS GLV-1h68...
متن کاملMatrix metalloproteinases-1 and -8 improve the distribution and efficacy of an oncolytic virus.
Oncolytic viral vectors show enormous potential for the treatment of many solid tumors. However, these vectors often suffer from insufficient delivery within tumors, which limits their efficacy in both preclinical and clinical settings. We have previously shown that tumor collagen can significantly hinder diffusion, and that its degradation can enhance the distribution and efficacy of an oncoly...
متن کاملSerotype Chimeric Human Adenoviruses for Cancer Gene Therapy
Cancer gene therapy consists of numerous approaches where the common denominator is utilization of vectors for achieving therapeutic effect. A particularly potent embodiment of the approach is virotherapy, in which the replication potential of an oncolytic virus is directed towards tumor cells to cause lysis, while normal cells are spared. Importantly, the therapeutic effect of the initial vira...
متن کاملCancer virotherapy: Targeting cancer cells by microRNA mechanism for selective replication of oncolytic viruses in these cells
Cancer, as one of the most serious public health problems, is the second-leading cause of death in the world after cardiovascular disease. The number of patients and the resulting mortality are increasing worldwide; therefore, early diagnosis, prevention, and effective treatment of cancer are very important. Current treatments such as chemotherapy and radiation therapy are often non-selective a...
متن کامل