24 April 2018
The future of cancer treatment?
Published online 18 July 2017
Self-assembling nanoparticles could pave a potentially promising therapeutic route.
A new polyprodrug, which self-assembles into stable nanoparticles in response to reactive oxygen species, shows targeted tumour treatment, shows a new study1.
The development and application of nanotherapeutics, which provide safer, more effective drug delivery, addresses the limits of conventional chemotherapy, including severe side effects, drug resistance, and short circulation lives.
Current approved nanoparticle delivery systems include Doxil (liposomal doxorubicin), Abraxane (nanoparticle albumin-bound paclitaxel), and Genexol-PM (paclitaxel-loaded polymer micelle).
However, their use does not always translate to an improved survival of cancer patients, due to premature drug release during nanoparticle preparation and storage or nanoparticle circulation in blood, lack of specific tumour tissue/cell targeting, and poor tumour tissue penetration.
An international research team, including a researcher from King Abdulaziz University, has now addressed these limitations with polyprodrug,
According to Xiaoding Xu, first author of the study published in Advanced Materials, polyprodrug are anticancer drug molecules, which are polymerized with cleavable linker to form a polymer and are highly responsive to reactive oxygen species (ROS).
This allows the targeted release of these drugs within the tumour, which has a high ROS level. The polyethylene glycol outer shell of the polyprodug prolongs blood circulation, while the surface-bound peptide enhances tumour targeting and tissue penetration. The ROS-responsive polyprodrug nanoparticles efficiently inhibited tumour growth in a xenograft tumour model.
This new platform can be applied to effectively treat various solid tumours.
Xu says that that their design concept could promote the development of a variety of new polyprodrugs from different therapeutic drugs, such as doxorubicin, cytarabine, dexamethasone, and therapeutic peptides. This could pave the way for the development of next-generation drug delivery systems for clinical applications.
“Further research under consideration includes therapeutic efficacy in advanced animal models such as orthotopic model, genetically engineering mouse model, and patient-derived xenograft model, and pharmacokinetics and toxicity evaluation in large animals,” says Xu.
- Xu, X. et al. ROS-responsive polyprodrug nanoparticles for triggered drug delivery and effective cancer therapy. Adv. Mater. http://dx.doi.org/10.1002/adma.201700141 (2017).