Considering the fact that iRGD (tumor-homing peptide) demonstrates tumor-targeting and tumor-penetrating activity, and that B16-F10 (murine melanoma) cells overexpress both αv integrin receptor and neuropilin-1 (NRP-1), the purpose of this study was to prepare a novel doxorubicin (DOX)-loaded, iRGD-modified, sterically-stabilized liposome (SSL) (iRGD-SSL-DOX) in order to evaluate its antitumor ...

We have shown that sterically stabilized (Stealth) liposomes (SL), can accumulate in the extracellular space within tumors, and may improve pharmacokinetics and therapeutic efficacy of encapsulated doxorubicin (SL-DOX). When SL-DOX were incubated in vitro at different temperatures with 50% bovine serum, approximately 20% of the encapsulated DOX was released at 42 degrees C within 1 min, compare...

The long-term usage of doxorubicin (DOX) is largely limited due to the development of severe cardiomyopathy. Many studies indicate that DOX-induced cardiac injury is related to reactive oxygen species generation and ultimate activation of apoptosis. The role of novel mitochondrial fission protein 1 (Mtfp1) in DOX-induced cardiotoxicity remains elusive. Here, we report the pro-mitochondrial fiss...

To determine the role of cyclooxygenase (COX)-2 in anthracycline-induced cardiac toxicity, we administered doxorubicin (Dox) to mice with genetic disruption of COX-2 (COX-2-/-). After treatment with Dox, COX-2-/- mice had increased cardiac dysfunction and cardiac cell apoptosis compared with Dox-treated wild-type mice. The expression of the death-associated protein kinase-related apoptosis-indu...

Previous reports have demonstrated that the second-generation tetracycline derivative doxycycline (DOX) interrupts mitochondrial proteostasis and physiology, inhibits proliferation of many cell types, and induces apoptosis. However, the effects of DOX, which is widely used in porcine husbandry by feed, on the porcine intestinal epithelium are unclear. In this study, we demonstrated that DOX dam...

Dexrazoxane [(DZR), ADR 529, ICRF-187] ameliorates doxorubicin (DOX)-induced cardiotoxicity in animals, and is recommended as a cardioprotectant in patients receiving cumulative doses of DOX above 300 mg/m2. A DZR:DOX dose ratio of 10:1 is recommended based on studies in patients receiving 50 mg/m2. Since DOX may be used at much higher doses in certain clinical settings, we evaluated the abilit...

Doxorubicin (DOX)-induced cardiomyopathy has been found to be associated with impaired Ca(2+) handling in the sarcoplasmic reticulum (SR), leading to reduced cardiac function. We have recently demonstrated that expression of mRNA encoding sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2), a major Ca(2+) transport protein in SR, is markedly decreased in DOX-treated hearts. To extend this obs...

Doxorubicin (DOX), an anthracycline used to treat a variety of cancers, is known to generate intracellular reactive oxygen species. Moreover, many patients who have undergone chemotherapy complain of cognitive dysfunction often lasting years after cessation of the chemotherapy. Previously, we reported that intraperitoneal administration of DOX led to elevated TNF-α and oxidative stress in the p...

Nanocarriers have recently emerged as an attractive platform for the delivery of various types of therapeutics including anticancer agents. Previously, we developed an improved TPGS delivery system (PEG5K-VE2) which demonstrated improved colloidal stability and greater in vivo antitumor activity. Nevertheless, the application of this system is still limited by a relatively low drug loading capa...

Parkinson's disease is a neurodegenerative condition involving the death of dopaminergic neurons in the substantia nigra. Dopamine D(1) receptor agonists are potential alternative treatments to current therapies that employ L-DOPA, a dopamine precursor. We evaluated the pharmacological profiles of the enantiomers of a novel dopamine D(1) receptor full agonist, doxanthrine (DOX) at D(1) and alph...