A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality.
In the present study, a new bubble-forming material (carboxymethyl hexanoyl chitosan, CHC), together with superparamagnetic iron oxide (SPIO) nanoparticles, was employed to prepare image-guided bubbles for efficiently encapsulating and delivering hydrophobic agents to kill tumor cells. The results showed that CHC could be used for preparing not only micronized bubbles (CHC/SPIO MBs) to exhibit ultrasound imaging functionality but also nanosized bubbles (CHC/SPIO NBs) to exhibit magnetic resonance T2 image contrast. It was found that the amounts of SPIO nanoparticles and hexane during preparation process were the key factors to obtaining CHC/SPIO NBs. Most importantly, under in vitro cell culture conditions with the same amount of camptothecin (CPT) and therapeutic sonication, CPT-loaded CHC/SPIO NBs demonstrated more significant transcellular delivery and cytotoxicity than free CPT. Subsequently, an intratumoral injection was proposed for the in vivo administration of hydrophobic-agent-loaded CHC/SPIO NBs. After injection, the distribution of a hydrophobic dye (DiR, an agent with near-infrared (NIR) fluorescence used as a model drug) released from the CHC/SPIO NBs was tracked by an NIR imaging technique. A significant tumor-specific accumulation was observed in the mouse that received the DiR-loaded CHC/SPIO NBs; the same was not observed in the mouse that received the free dye (without incorporating with CHC/SPIO NBs). It is expected, in the future, both the dose of the therapeutic agent administered and its side effects can be significantly lowered by using novel CHC/SPIO NBs together with local delivery (intratumoral injection), targeted imaging and enhanced cellular uptake of the drug.
Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC.
Pei-Sin
PS
Yang
Department of Orthopaedic Surgery, Taipei City Hospital, Taipei, Taiwan, ROC.
Fu-I
FI
Tung
Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC.
Hsiao-Ping
HP
Chen
Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: andyliudpum@yahoo.com.tw.
Tse-Ying
TY
Liu
Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC.
Yi-Ying
YY
Lin
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D005260:Female; D005740:Gases / Q000138:chemical synthesis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*
D003287:Contrast Media; D003911:Dextrans; D005740:Gases; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10
Bubble-forming materials; Carboxymethyl hexanoyl chitosan; SPIO; Sonication; Theranostic