Abstract
Selectively targeted drug delivery systems are preferable chemotherapeutic platforms, as they specifically deliver the drug cargo into tumor cells, while minimizing untoward toxic effects. However, these delivery systems suffer from insufficient encapsulation efficiency (EE), encapsulation capacity (EC), and premature drug release. Herein, we coencapsulated paclitaxel (PTX) and Jasmine oil (JO) within PEG-PCL nanoparticles (NPs), with an average diameter < 50 nm, selectively targeted to non-small cell lung cancer (NSCLC) cells, via S15-aptamer (APT) decoration. JO was selected as an “adhesive” oily core to enhance PTX entrapment, as JO and PTX share similar hydrophobicity and terpenoid structure. JO markedly enhanced EE of PTX from 23% to 87.8% and EC from 35 ± 6 to 74 ± 8 µg PTX/mg PEG-PCL. JO also markedly increased the residual amount of PTX after 69 h, from 18.3% to 65%. Moreover, PTX cytotoxicity against human NSCLC A549 cells was significantly enhanced due to the co-encapsulation with JO; the IC50 value for PTX encapsulated within JO-containing APT-NPs was 20-fold lower than that for APT-NPs lacking JO. Remarkably, JO-containing APT-NPs displayed a 6-fold more potent cell-killing, relatively to the free-drug. Collectively, these findings reveal a marked synergistic contribution of JO to the cytotoxic activity of APT-NP-based systems, for targeted PTX delivery against NSCLC, which may be readily applied to various hydrophobic chemotherapeutics.
Highlights
Lung cancer remains the leading cause of cancer-related death worldwide [1]
APT-decorated PP NPs, targeting Nonsmall cell lung cancer (NSCLC) cells, was shown to substantially reduce PTX drug doses required for a therapeutic effect
We demonstrated that Jasmine oil (JO) in the core of NPs enhanced both EE and Encapsulation Capacity (EC) of PTX, while diminishing premature drug release, resulting in a synergistically enhanced cytotoxic activity
Summary
Lung cancer remains the leading cause of cancer-related death worldwide [1]. Nonsmall cell lung cancer (NSCLC) is the prevalent lung cancer type, responsible for over 85%of lung cancer cases [2]. Lung cancer remains the leading cause of cancer-related death worldwide [1]. Nonsmall cell lung cancer (NSCLC) is the prevalent lung cancer type, responsible for over 85%. Of lung cancer cases [2]. Patients with NSCLC are treated with chemotherapy, whereas advanced NSCLC treatment is based on combination chemotherapy, radiotherapy and/or surgery [3]. Cancer recurrence is frequently observed [4]. Paclitaxel (PTX) is the main first-line chemotherapeutic drug used for the treatment of advanced NSCLC [5]. PTX, an anti-microtubule cytotoxic drug, inflicts severe untoward toxic effects, including neutropenia and peripheral neuropathy, due to the lack of specificity, and low water-solubility requiring the use of surfactant-solvent mixtures, like
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