Mechanism of laser-induced drug delivery in tumors

Penetration of anti-cancer drugs (especially macromolecular agents) from blood in tumor cells is limited due to the presence of physiological barriers: tumor capillary wall, slow diffusion in the interstitium, and cancer cell membrane. Interaction of exogenous nano- or microparticles with laser or ultrasonic radiation may enhance drug delivery in tumor cells due to laser- or ultrasound-induced cavitation. Our previous studies demonstrated enhanced delivery of model macromolecular anti-cancer drugs in tissues in vitro when laser or ultrasonic radiation is applied. In this paper, we studied laser-induced cavitation in suspension of strongly absorbing particles and laser-enhanced drug delivery in human colon tumors of nude mice in vivo. Cavitation kinetics and thresholds were measured for carbon and colored polystyrene particle suspensions. Histological examination of control and irradiated tumors with fluorescent microscopy demonstrated that Q-switched Nd:YAG laser irradiation enhances delivery of a model macromolecular drug (FITC-dextran) in tumor blood vessel and interstitium. Enhanced delivery of an anti-cancer drug (5-FU) that is currently used in clinics resulted in tumor necrosis and inhibited tumor growth. Results of our studies suggest that the drug delivery enhancement is due to cavitation produced by local heating of particles with pulsed laser radiation.

[1]  Rinat O. Esenaliev,et al.  Laser ablation of aqueous solutions with spatially homogeneous and heterogeneous absorption , 1994 .

[2]  E K Rowinsky,et al.  Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model. , 1999, Cancer research.

[3]  Donald R Uhlmann,et al.  Mechanism of Inclusion Damage in Laser Glass , 1970 .

[4]  Steven L. Jacques,et al.  Transient and permanent cavitation in collagen gels by laser-induced thermoelastic pressure waves , 1996, Photonics West.

[5]  R. Hoffman,et al.  5-FU-induced apoptosis correlates with efficacy against human gastric and colon cancer xenografts in nude mice. , 1997, Anticancer research.

[6]  B. Evers,et al.  Neurotensin stimulates growth of colon cancer. , 1992, Surgical oncology.

[7]  M De Brabander,et al.  Levamisole plus 5-fluorouracil inhibits the growth of human colorectal xenografts in nude mice. , 1992, European journal of cancer.

[8]  Rinat O. Esenaliev,et al.  Interaction of radiation with microparticles for enhancement of drug delivery in tumors , 1999, Photonics West - Biomedical Optics.

[9]  B. Evers,et al.  Fetal and neoplastic expression of the neurotensin gene in the human colon. , 1996, Annals of surgery.

[10]  H Tanino,et al.  Recombinant human interferon alpha-2a increases the antitumor activity of 5-fluorouracil on human colon carcinoma xenograft Co-4 without any change in 5-FU pharmacokinetics. , 1995, Anticancer research.

[11]  B. Curti.  Physical barriers to drug delivery in tumors. , 1993, Critical reviews in oncology/hematology.

[12]  R K Jain,et al.  Delivery of Molecular Medicine to Solid Tumors , 1996, Science.

[13]  R K Jain,et al.  Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. , 1990, Journal of the National Cancer Institute.

[14]  J. Givel,et al.  Interferon alpha and 5'-deoxy-5-fluorouridine in colon cancer: effects as single agents and in combination on growth of xenograft tumours. , 1994, European journal of cancer.

[15]  F. Zunino,et al.  Effects of 5-FU and cis-DDP Combination on Human Colorectal Tumor Xenografts , 1989, Tumori.