Paclitaxel-loaded solid lipid nanoparticles modified with Tyr-3-octreotide for enhanced anti-angiogenic and anti-glioma therapy.
Somatostatin receptors (SSTRs) especially subtype 2 (SSTR2) are overexpressed in glioma. By taking advantage of the specific expression of SSTR2 on both glioma neovasculature endothelial cells and glioma cells, we constructed Tyr-3-octreotide (TOC)-modified solid lipid nanoparticles (SLN) loaded with paclitaxel (PTX) to enable tumor neovasculature and tumor cells dual-targeting chemotherapy. In this work, a TOC-polyethylene glycol-lipid (TOC-PEG-lipid) was successfully synthesized and used as a targeting molecule to enhance anticancer efficacy of PTX loaded sterically stabilized lipid nanoparticles. The prepared PTX-loaded SLN modified with TOC (PSM) was characterized by standard methods. In rat C6 glioma cells, PSM improved PTX induced apoptosis. Both tube formation assay and CD31 staining of treated orthotopic glioma tissues confirmed that PSM significantly improved the antiangiogenic ability of PTX in vitro and in vivo, respectively. Radiolabelled PSM achieved a much higher and specific accumulation within the glioma as suggested by the biodistribution and imaging studies. Furthermore, PSM exhibited improved anti-glioma efficacy over unmodified nanoparticles and Taxol in both subcutaneous and orthotopic tumor models. These findings collectively indicate that PSM holds great potential in improving the efficacy of anti-glioma therapy.



Somatostatin receptors (SSTRs) especially subtype 2 (SSTR2) are overexpressed in various mammalian cancer cells. Proliferating endothelial cells of neovasculature also express SSTR2. Tyr-3-octreotide (TOC) is a known ligand for SSTR2. We have successfully prepared paclitaxel-loaded solid lipid nanoparticles modified with TOC (PSM) having diameter less than 100nm. We found that PSM improved anti-cancer efficacy of paclitaxel in SSTR2 positive glioma of rats. This improved anti-glioma efficiency of PSM can be attributed to dual-targeting (i.e. tumor cell and neovasculature targeting) efficiency of PSM and promoted anti-cancer drug accumulation at tumor site due to TOC modification of solid lipid nanoparticles. This particular study aims at widening the scope of octreotide-derivative modified nanocarrier by exploring dual-targeting potential of PSM.
Department of Infectious Diseases and Immunology (Nuclear Medicine Division), CSIR-IICB, 4 Raja S C Mullick Road, Kolkata 700032, India. Electronic address: samu.jubph@gmail.com.
Indranil
I
Banerjee
Department of Infectious Diseases and Immunology (Nuclear Medicine Division), CSIR-IICB, 4 Raja S C Mullick Road, Kolkata 700032, India.
Kakali
K
De
Department of Infectious Diseases and Immunology (Nuclear Medicine Division), CSIR-IICB, 4 Raja S C Mullick Road, Kolkata 700032, India.
Dibyanti
D
Mukherjee
School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India.
Goutam
G
Dey
Radiopharmaceuticals Laboratory, Regional Centre, Board of Radiation and Isotope Technology, Variable Energy Cyclotron Centre, 1/AF, Bidhan Nagar, Kolkata 700064, India.
Sankha
S
Chattopadhyay
Saha Institute of Nuclear Physics, Kolkata 700064, India.
Manabendra
M
Mukherjee
School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India.
Mahitosh
M
Mandal
Division of Pharmaceutics, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
Amal Kumar
AK
Bandyopadhyay
Regional Radiation Medicine Centre, Thakurpukur Cancer Research Centre, Kolkata 700063, India.
Amit
A
Gupta
Regional Radiation Medicine Centre, Thakurpukur Cancer Research Centre, Kolkata 700063, India.
Santanu
S
Ganguly
Department of Infectious Diseases and Immunology (Nuclear Medicine Division), CSIR-IICB, 4 Raja S C Mullick Road, Kolkata 700032, India. Electronic address: mridulamisra@iicb.res.in.
Mridula
M
Misra
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
D004337:Drug Carriers; D008055:Lipids; C045210:3-Tyr-octreotide; D017239:Paclitaxel; D015282:Octreotide
Dual-targeting; Glioma therapy; Paclitaxel; Solid lipid nanoparticles; Tyr-3-octreotide