Chronic inflammation is closely related to the development, deterioration, and metastasis of tumors. Recently, many studies have shown that down-regulating the expression of inflammation by blocking nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription 3 (STAT3) pathways could significantly inhibit tumor growth and metastasis. The combined application of curcumin (CUR) and celecoxib (CXB) has been proven to exert a synergistic antitumor effect via inhibiting the activation of NF-kappa B and STAT3. TAT-NBD (TN) peptide, a fusion peptide of NF-kappa B essential modulator (NEMO)-binding domain peptide (NBD) and cell-penetrating peptide (TAT), can selectively block NF-kappa B activating pathway resulting in tumor growth inhibition. In the present study, a novel TN-modified liposome coloading both CXB and CUR (TN-CCLP) at a synergistic ratio was first constructed with the property of synchronous release, then hyaluronic acid (HA) as CD44 targeting moiety was coated on the surface of the cationic liposome via electrostatic interaction to prepare the anionic HA/TN-CCLP. In vitro results of cytotoxicity, macrophage migration inhibition, and anti-inflammation efficacy revealed that TN-CCLP and HA/TN-CCLP were significantly superior to TN-LP and CCLP, while TN-CCLP exhibited better effects than HA/TN-CCLP due to higher cellular uptake ability. Different from in vitro data, after systematically treating 4T1 breast tumor-bearing mice, HA/TN-CCLP exerted the most striking effects on anti-inflammation, inhibition of macrophage recruitment, and antitumor because of the longest circulation time and maximum tumor accumulation. In particular, HA/TN-CCLP could availably block the lung metastasis of breast cancer. Taken together, the novel CD44 targeted TN-CCLP exhibited the potential for inhibiting tumor development and metastasis through improving inflammatory infiltration of tumor tissue.
[1]Fudan Univ, Key Lab Smart Drug Delivery, Sch Pharm, Minist Educ,Dept Pharmaceut, Shanghai 200032, Peoples R China.
[2]Chinese Acad Sci, Shanghai Inst Materia Med, Shanghai 201203, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China.
[4]Fudan Univ, Shanghai Pudong Hosp, Dept Hematol, Shanghai 201399, Peoples R China.
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