When it comes to fightingcancer, the goal is to deliver high doses of drug molecules tothe tumor for maximumefficiency while the organs themselves do not receive anybyproduct. To achievethis, single-walled carbon nanotubes (SWNT) are injected andthey can effectivelyshuttle certain biomolecules into cells directly. They are able toshuttle drugs, peptides,proteins, plasmid DNA, and RNA using endocytosis. Theintrinsic near-IR (NIR)light absorption property has been used to destroy cancer cells invitro and NIRphotoluminescence has been used for imaging and probing. Methods and MaterialsThe experiment began withthe functionalization of SWNTs with phospholipid-branchedpolyethylene glycol. Nextis the paclitaxel (PTX) conjugation.
PTX was modified bysuccinic anhydride andcarboxyl acid was added on the molecule. After the SWNT-PTXwas purified it wasfiltrated through MWCO filters and extensive washing the removeunconjugated PTX. Celltoxicity assay followed. Breast cell cancer was cultured instandard medium. It wastreated in PEGylated PTX (PEG-PTX) concentrations, SWNTPTXconcentrations, and Taxolfor 3 days. Cell viability was measure afterwards. Nextwas animal model andtreatment.
Mice were used for treatment for tumor volume. Tumorslice staining and imagingwas next. Tumor slices were cut after frozen in OCT mediumand stained withfluorescent terminal. The Raman mapping image of tumor slices wasinjected with SWNT-PTXinto mice.
To obtain a Raman image, the SWNT G-bandRaman intensity wasplotted on X and Y positions across the liver slice. Next werePharmacokinetics andbiodistribution studies. Blood circulation was measured bydrawing 10 micro litersfrom the vein of the tumor-free mice after the injection SWNTPTX,Taxol, or PEG-PTX. Thesamples of blood were dissolved in lysis buffer with briefsonication. The Ramanmethod was used to measure the concentration of SWNTs in theblood. Necropsy, bloodchemistry, and histology study followed. Then a statisticalanalysis was done.Results and DiscussionThe results showed thatthere were significant differences of the blood biodistribution ofthe three formulation ofPTX.
SWNT-PTX showed noticeable PTX activity in the bloodwithin 2 hours ofinjection. Whereas PTX levels in the blood was much lower in the Taxoland PEG-PTX concentration.Most importantly, SWNT-PTX afforded a much higher PTXuptake than Taxol andPEG-PTX. This allows for higher drug delivery efficiency to thetumor. This means that alower injected dose of the SWNT-PTX can be used for tumorsuppression. This willlower toxic side effects to the healthy organs and tissues.
Afterinvestigating thebiodistribution and dissecting the mouse and investigating the tissue,results come out the samein regards to the SWNT-PTX. Comments and Critics Strength and advantages:Single-walled carbonnanotubes (SWNT) delivery of paclitaxel (PTX) lowers tumor growth whilepreventing high amounts of toxicity to the healthy organs. The key to thesuccess of the SWNT is the higher tumor suppression efficiency due to the10-fold higher tumor uptake of PTX afforded by SWNT carriers. Both the PTX andSWNT filter out of the body with no toxicity present in the body when evaluatedby biodistribution.Weakness anddisadvantages:Single-walled carbonnanotubes (SWNT) have short lives. In addition, the high uptake of SWNT-PTX inthe Reticuloendothelial System (RES) affects certain organs such as the liverand spleen. These affects could be harmful over a long period of time.
WhilePTX filters out of the body quite quickly, as found in the feces and urine ofthe rats tested,Single-walled carbonnanotubes (SWNT) seem to have limited weaknesses. I furthered my researchbeyond this article (as cited) and could find nearly no down side to thismethod of drug delivery. The SWNT have short lives within the body, which wouldbe a major negative if they did not deliver enough of the drug in time.However, they deliver the paclitaxel (PTX) drug within 2 hours. This seemed toogood to be true so I looked beyond the main article cited and found similarresearch done with similar results (2 hours and 30 minutes). The main concernwhen dealing with cancer and tumors is to deliver enough of the given drugwhile causing little to no harm to the healthy organs, especially to the organsthat’s role is filtration, and needless to say that this method of drugdelivery does just that.
SWNT-PTX that was taken up by the RES organs and wasdissociated via ester cleavage. There were large amounts of PTX that were foundin the feces and urine of the mice tested. Yet the SWNT remained for weeks andeven months. Perhaps while the SWNT “waits” to be filtered out of the body,they could be of more use than just delivering the PTX, such as imaging. WithRaman and photoluminescence, valuable means of tracking and detecting tofurther understand in vivo behavior and drug delivery efficacy is possible.