Dual-function nanostructured lipid carriers to deliver IR780 for breast cancer treatment: Anti-metastatic and photothermal anti-tumor therapy.
Cancer treatments that use a combination of approaches with the ability to affect multiple disease pathways have proven highly effective. The present study reports on CXCR4-targeted nanostructured lipid carriers (NLCs) with a CXCR4 antagonist AMD3100 in the shell (AMD-NLCs). AMD-NLCs loaded with IR780 (IR780-AMD-NLCs) reduced the invasiveness of cancer cells, while simultaneously mediating efficient tumor targeting and photothermal therapeutic outcomes. We present the combined effect of encapsulated IR780 on photothermal therapy and of the AMD3100 coating on tumor targeting, CXCR4 antagonism and inhibition of cancer cell invasion and breast cancer lung metastasis in vitro and in vivo. IR780-AMD-NLCs exhibited excellent IR780 loading capacity and AMD3100 coating efficiency. The photothermal properties of IR780 were improved by encapsulation in NLCs. The encapsulated IR780 displayed better heat generating efficiency than free IR780 when exposed to repeated laser irradiation. CXCR4 antagonism and cell invasion assays confirmed that IR780-AMD-NLCs fully inhibited CXCR4 while IR780-NLCs did not function as CXCR4 antagonists. AMD3100-coated NLCs accumulated at high levels in tumors, as judged by in vivo imaging and biodistribution assays. Furthermore, CXCR4-targeted NLCs exhibited an encouraging photothermal anti-tumor effect as well as anti-metastatic efficacy in vivo. These findings suggest that this simple and stable CXCR4-targeted IR780 delivery system holds great promise for prevention of metastasis and for photothermal treatment of tumors.



Breast cancer is a major threat to human health, it is not the primary breast tumor that is ultimately responsible for the majority of deaths, but the tumor metastasis, which frequently follows a specific pattern of dissemination. We report development of a novel dual-function nanostructured lipid carrier (NLC) for breast cancer treatment. The carrier encapsulates NIR dye IR780 in its core and contains antagonist of the chemokine receptor CXCR4 in its shell. Our results show that by combining the CXCR4 antagonism with photothermal effect of the dye leads to remarkable antitumor and antimetastatic activity in syngeneic orthotopic model of metastatic breast cancer. Furthermore, the developed system also shows a theranostic potential due to NIR fluorescence of the encapsulated dye.
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, Pharmaceutical University, Nanjing 210009, China.
Huipeng
H
Li
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, Pharmaceutical University, Nanjing 210009, China.
Kaikai
K
Wang
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, Pharmaceutical University, Nanjing 210009, China.
Xue
X
Yang
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, Pharmaceutical University, Nanjing 210009, China.
Yiwen
Y
Zhou
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, Pharmaceutical University, Nanjing 210009, China.
Qineng
Q
Ping
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, Pharmaceutical University, Nanjing 210009, China; Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: david.oupicky@unmc.edu.
David
D
Oupicky
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, Pharmaceutical University, Nanjing 210009, China. Electronic address: sun_minjie@163.com.
Minjie
M
Sun
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001596:Benzylamines; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D000080027:Cyclams; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D005260:Female; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry; D008055:Lipids / Q000737:chemistry / Q000528:radiation effects; D008081:Liposomes / Q000737:chemistry* / Q000528:radiation effects; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome
C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D000970:Antineoplastic Agents; D001596:Benzylamines; D000080027:Cyclams; D003692:Delayed-Action Preparations; D006571:Heterocyclic Compounds; D007211:Indoles; D008055:Lipids; D008081:Liposomes; D053769:Nanocapsules; D017319:Photosensitizing Agents; C088327:plerixafor
AMD3100; Anti-metastatic; IR780; Nanostructured lipid carrier; Photothermal antitumor