Figure S1 from Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies

Supplementary Figure S1. Chemical structures of paclitaxel, docetaxel, and cabazitaxel.</p

Supplementary Methods from Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies

Supplementary methods for nanonparticle characterization, cell assays and histological analyses of tumors.</p

Table S1 from Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies

Supplementary Table S1. Hematology measurements for the mice after the treatment with saline, cabazitaxel and dCTX NPs. The blood samples were collected on day 0, 6, 11, and 15 post-administration. The data are presented as the means {plus minus} SD (n = 5).</p

Figure S4 from Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies

Supplementary Figure S4. Cellular uptake of dCTX NPs in Hela/DTX cells. The cells were treated with free DiI and DiI@dCTX NPs and visualized by confocal laser scanning microscope (CLSM). The red fluorescent signal represented the DiI dye in cells. The cell lysosomes and nuclei were stained with LysoTracker Green NDN-26 (green) and Hoechst 33342 (blue), respectively. The scale bars represent 20 μm in length.</p

Figure S2 from Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies

Supplementary Figure S2. The cytotoxicity of dCTX NPs compared with cabazitaxel against cancer cell lines in vitro. Analysis (A) and quantification (B) of apoptosis of HeLa and A549 cells after the treatment with dCTX NPs for 48 h. The drug concentrations used to treat HeLa and A549 cells were 16 and 4 nM, respectively.</p

Figure S3 from Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies

Supplementary Figure S3. The cytotoxicity of dCTX NPs compared with cabazitaxel against cancer cell lines in vitro. Analysis (A) and quantification (B) of cell cycle of HeLa and A549 cells after the treatment with dCTX NPs for 48 h. The drug concentrations used to treat HeLa and A549 cells were 8 and 2 nM, respectively.</p

Self-Assembled Gemcitabine Prodrug Nanoparticles Show Enhanced Efficacy against Patient-Derived Pancreatic Ductal Adenocarcinoma

Effective new therapies for pancreatic ductal adenocarcinoma (PDAC) are desperately needed as the prognosis of PDAC patients is dismal and treatment remains a major challenge. Gemcitabine (GEM) is commonly used to treat PDAC; however, the clinical use of GEM has been greatly compromised by its low delivery efficacy and drug resistance. Here, we describe a very simple yet cost-effective approach that synergistically combines drug reconstitution, supramolecular nanoassembly, and tumor-specific targeting to address the multiple challenges posed by the delivery of the chemotherapeutic drug GEM. Using our developed PUFAylation technology, the GEM prodrug was able to spontaneously self-assemble into colloidal stable nanoparticles with sub-100 nm size on covalent attachment of hydrophobic linoleic acid via amide linkage. The prodrug nanoassemblies could be further refined by PEGylation and PDAC-specific peptide ligand for preclinical studies. In vitro cell-based assays showed that not only were GEM nanoparticles superior to free GEM but also the decoration with PDAC-homing peptide facilitated the intracellular uptake of nanoparticles and thereby augmented the cytotoxic activity. In two separate xenograft models of human PDAC, one of which was a patient-derived xenograft model, the administration of targeted nanoparticles resulted in marked inhibition of tumor progression as well as alleviated systemic toxicity. Together, these data unequivocally confirm that the hydrophilic and rapidly metabolized drug GEM can be feasibly transformed into a pharmacologically efficient nanomedicine through exploiting the PUFAylation technology. This strategy could also potentially be applied to rescue many other therapeutics that show unfavorable outcomes in the preclinical studies because of pharmacologic obstacles

Supramolecular Engineering of Molecular Inhibitors in an Adaptive Cytotoxic Nanoparticle for Synergistic Cancer Therapy

Combinatorial regimens that rationally pair molecular inhibitors with standard cytotoxic chemotherapeutics are used to improve therapeutic outcomes. Simultaneously engineering these therapies within a single nanocarrier that spans cytotoxic, antiangiogenic, and anti-invasive mechanisms and that enables the delivery of unique drug combinations remains a technical challenge. In this study, we developed a simple and broadly applicable strategy in which ultrastable cytotoxic nanoparticles with an established excellent antitumor efficacy and π-rich inner core structure supramolecularly stabilized the antiangiogenic molecular inhibitor apatinib to create a synergistic drug delivery system (termed sTKI-pSN38). This small-sized nanoparticle accomplished the sequential release of both encapsulated drugs to exert antimetastatic, antivascular, and cytotoxic activities simultaneously. In xenograft models of hepatocellular carcinoma, a single intravenous administration of sTKI-pSN38 elicited robust and durable tumor reduction and suppressed metastasis to lymph nodes. Interestingly, sTKI-pSN38 treatment alleviated intratumoral hypoxia, which could contribute to impaired tumor metastasis and reduced drug resistance. Collectively, this nanotherapeutic platform offers a new strategy for cancer therapy by simply engineering a drug cocktail in conventional nanoparticles and by enabling the spatiotemporal modulation of drug release to enhance the synergy of the combined drugs

Figure S5-S6 from New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

In vivo drug plasma concentration-time profile and drug tissue biodistribution</p

Figure S2 from New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

In vitro cytotoxicity of nanodrugs against human breast cancer MDA-MB-231 cells and human colorectal carcinoma LoVo cells</p