Abstract
The inherent features of small interfering RNA (siRNA), including a relatively high molecular weight, negative charge, and hydrophilic nature, lead to the widespread use of cationic polymers and lipid-based nanocarriers, which might induce potential cytotoxicity, thus limiting their clinical application. Here, we report a facile strategy for changing the inherent features of siRNA molecules by achieving hydrophobization. We found that the simple mixing of siRNA and doxorubicin hydrochloride (DOX·HCl) could form a hydrophobic complex, which was readily encapsulated into noncationic PEG- b-PLA micelles for systemic delivery. In addition to delivering DOX·HCl, this strategy could be extended to deliver other hydrochloride forms of anticancer drugs with large hydrophobic domains. This facile strategy efficiently avoids the use of cationic nanocarriers, providing a new avenue for siRNA delivery.
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