A Molecular Recognition Approach To Synthesize Nucleoside Analogue Based Multifunctional Nanoparticles for Targeted Cancer Therapy

Abstract

Tumor-targeted drug delivery with simultaneous cancer imaging is highly desirable for personalized medicine. Herein, we report a supramolecular approach to design a promising class of multifunctional nanoparticles based on molecular recognition of nucleobases, which combine excellent tumor-targeting capability via aptamer, controlled drug release, and efficient fluorescent imaging for cancer-specific therapy. First, an amphiphilic prodrug dioleoyl clofarabine was self-assembled into micellar nanoparticles with hydrophilic nucleoside analogue clofarabine on their surface. Thereafter, two types of single-stranded DNAs that contain the aptamer motif and fluorescent probe Cy5.5, respectively, were introduced onto the surface of the nanoparticles via molecular recognition between the clofarabine and the thymine on DNA. These drug-containing multifunctional nanoparticles exhibit good capabilities of targeted clofarabine delivery to the tumor site and intracellular controlled drug release, leading to a robust and effective antitumor effect in vivo.

Stressing the Role of DNA as a Drug Carrier: Synthesis of DNA–Drug Conjugates through Grafting Chemotherapeutics onto Phosphorothioate Oligonucleotides

“…Due to the diblock design of the DNA strand, regular polyT segments with retained molecular recognition capability at the micelle corona can be used to further hybridize with functional nucleic acids, such as aptamers and dye‐labeled DNA strands, via Watson–Crick base pairing, providing the SNA structure with targeting and imaging functionalities. Although nanosized DDSs have been reported to possess enhanced drug accumulation through an enhanced permeation and retention effect, the presence of this passive targeting mechanism in clinical tumor models remains unclear .…”

“…To confirm the tumor targeting capability in vitro, both flow cytometry and confocal laser scanning microscopy (CLSM) were used to evaluate the cell uptake efficiency of PTX‐SNAs loaded with or without the aptamer. Two tumor cell lines, including human breast cancer cells (MCF‐7) and human cervical tumor cells (HeLa) that overexpress nucleolin on the cell membrane, and a normal fibroblast cell line (L929) were incubated with FAM‐labeled nontargeting (FAM/PTX‐SNA) and targeting (FAM/AS1411/PTX‐SNA) PTX‐SNAs . As shown in Figure , both nontargeting and targeting PTX‐SNAs exhibited relatively high efficiency of cell internalization, which could be ascribed to the advantage of the SNA architecture .…”

Self‐Assembled Supramolecular Nanoparticles for Targeted Delivery and Combination Chemotherapy

“…[15] Carriers are usually amphiphilic molecules, macrocycles, or oligonucleotides. They can form vesicles, polymericn anoparticles, or DNA nanostructures in aqueous solution at room temperatureu nder gentle conditions via noncovalentm odes, such as hydrophilic interactions, [16][17][18] host-guest interactions, [17,19,20] and nucleic acid hybridization. [4,21,22] Therapeutic agentsa re generally loaded in the carriers by physicale ncapsulation, [23][24][25] electrostatic interactions, [9,26] and host-guesti nteractions.…”

“…[27][28][29] Nanostructures encapsulated only with drugs do not have targeting ability andb lood circulation ability,w hich usually need to be modified with functional molecules through noncovalent interactions. [18,30] These functional molecules, fore xample, enzymes, nucleic acids, and proteins, are integrated into nanostructures via noncovalent interactions, which may avoid the loss of biological activity.T herefore, af lexible and efficient It is challenging but imperative to merge imaging agentsa nd small molecule therapeutics into one nanoentity for diagnosis and treatment. Herein, we constructed polymericn anoparticles for targeted delivery and combination chemotherapy,w hich formed through host-guest interactions amongt hree elements:1 )b-cyclodextrinp olymer (poly-b-CD), as the backbone of nanoparticles;2 )two antitumor drugs-doxorubicin (DOX) and docetaxel (DTX);a nd 3) aptamersl abeled with adamantane and fluorescein( Ad-aptamer-FAM), as recognition elements.F irst, polymeric nanoparticles,t ermed self-assembled supramolecular nanoparticles (SSNPs),w ere formulated by combining hydrophobic DTX and DOX with poly-b-CD via host-guest interactions.…”

Tough Adhesion of Nucleobase‐Tackifed Gels in Diverse Solvents

“…[21][22][23][24] In our previous work, the nucleobase-tackified strategy was presented to successfully endow hydrogels with strong, multipurpose, durable, and antifatigue adhesive behavior only in the air. [21][22][23][24] In our previous work, the nucleobase-tackified strategy was presented to successfully endow hydrogels with strong, multipurpose, durable, and antifatigue adhesive behavior only in the air.…”