Nano-Cryosurgery: Advances and Challenges

Abstract

In clinics, the minimally invasive freezing therapy, commonly known as cryosurgery, has been increasingly used for the controlled destruction of tumor tissue. However, there are still many bottlenecks to impede the success of a cryosurgery. One of the most critical factors has been that insufficient or inappropriate freezing will not completely destroy the target tumor tissues, which as a result may lead to tumor regenesis and thus failure of treatment. In addition, the surrounding healthy tissues may suffer from serious freeze injury due to unavoidable release of a large amount of cold from the freezing probe. To resolve these challenges, we recently proposed a new strategy, termed as nano-cryosurgery, to improve freezing efficiency of the conventional cryosurgical procedure. The basic principle of this protocol is to deliver functional suspension of nanoparticles with favorable physical and/or chemical properties into the target tissues, which then serve as adjuvant or drug carrier either to maximize the freezing heat transfer process, regulate freezing scale, modify ice-ball formation orientation or prevent the surrounding healthy tissues from being frozen. In addition, introduction of nanoparticles during cryosurgery could also help better image the edge of a tumor as well as the margin of the iceball. The new therapy raised many critical fundamental as well as practical issues for solving. This review is dedicated to present a comprehensive review on multiscale fundamental phase change heat transfer issues thus involved. Attentions would span from micro-scale heat transfer in cellular scale to tissue level. Some related thermal physical effects of nanoparticles on the freezing process such as ice nucleation enhancement, water transport during freezing of a single cell will be discussed. Cryosurgical thermal management of using nanoparticles to modify thermal properties of the tissue-particle components, regulate the growth orientation and strength of an ice ball, enable a conformal tumor destruction in tissues with or without large blood vessels, etc. will be illustrated. Meanwhile, the fundamental issue for the transport of nanoparticle and its assisted drug delivery will be summarized. Theoretical modeling as well as experimental approaches for studying the micro/nano-scale heat transfer throughout the tissue or cell domain during nano-cryosurgery will be suggested. Some potential applications and possible challenges when nanotechnology meets cryosurgery will be outlined. The nano-cryosurgery is expected to help expand the boundary of the emerging frontier of nano-biomedical engineering.

Fe3O4 nanoparticles and cryoablation enhance ice crystal formation to improve the efficiency of killing breast cancer cells

“…Similar results were also observed in the analysis of cell apoptosis. Subsequently, we simulated the entire process of cryoablation in the presence of 100 μg/mL Fe 3 O 4 nanoparticles, confirming that the ice crystals were efficiently formed during the freezing and thawing process, which was considered to perform twice killing for MCF-7 breast cancer cells [25]. …”

Thermostability of Biological Systems: Fundamentals, Challenges, and Quantification

“…For example, TNF-α has been found to increase the thermal threshold of cryoinjury to prostate cancer cells from ~ -20 to 0 o C [200], which is significant because it indicates that all cancer cells could be killed in a frozen tumor iceball and it is much more convenient to monitor the size of the frozen tumor iceball (e.g., using ultrasonography) than the subzero temperature inside the iceball. Therefore, using therapeutic adjuvants such as TNF-α to augment cryoinjury and the controlled/targeted delivery of the adjuvants into tumor and tumor cells using nanotechnology have attracted more and more attention in the field of thermal destruction at cryogenic temperatures [201,219,220]. …”

Nanorobotic Applications in Medicine: Current Proposals and Designs

“…To date, some examples of what nanotechnology has enabled include the development of improved imaging techniques for higher sensitivity in detection of cancer and illness 2 , improved targeting of drug treatments 3 , decrease in the number of adverse effects of chemotherapy, and the enhanced effectiveness of other antineoplastic therapies such as cryotherapy 4 and ultrasound 5 . Outside of medicine, nanotechnology is also fueling developoments in agriculture 6 , energy 7 , electronics 8 , and many other fields.…”