Carriers that can afford tunable physical and structural changes are envisioned to address critical issues in controlled drug delivery applications. Herein, photo-responsive conjugated polymer nanoparticles (CPNs) functionalized with donor-acceptor Stenhouse adduct (DASA) and folic acid units for controlled drug delivery and imaging are reported. Upon visible-light (λ=550 nm) irradiation, CPNs simultaneously undergo structure, color, and polarity changes that release encapsulated drugs into the cells. The backbone of CPNs favors FRET to DASA units boosting their fluorescence. Notably, drug-loaded CPNs exhibit excellent biocompatibility in the dark, indicating perfect control of the light trigger over drug release. Delivery of both hydrophilic and hydrophobic drugs with good loading efficiency was demonstrated. This strategy enables remotely controlled drug delivery with visible-light irradiation, which sets an example for designing delivery vehicles for non-invasive therapeutics.
The adherence of serum protein on conjugated polymer is a major bottleneck in the application of the latter for selective sensing of small biomolecules in blood serum. In this report, we present new polyfluorenes with D-glucuronic acid appendage that is a nonreceptor for any serum protein, thereby providing a platform for selective sensing of free bilirubin in the clinically relevant range of <25 to >50 μmol/L in human blood serum. The appended D-glucuronic acid formed noncovalent interactions with bilirubin, which in conjunction with favorable spectral overlap between the polymers and bilirubin facilitated efficient FRET process in aqueous solutions. Addition of bilirubin resulted in the quenching of the polyfluorene emission with simultaneous appearance of bilirubin emission exhibiting visual emission color change from blue to light green. The polymer remained stable in serum even under severe basic conditions and exhibited high selectivity with visual sensitivity only toward free bilirubin in human serum in the presence of crucial interferences such as hemoglobin, proteins, biliverdin, glucose, cholesterol, and metal ions. Nanomolar sensing of bilirubin could also be demonstrated successfully using one of the D-glucuronic acid appended polymer (PF-Ph-GlcA), which could sense ∼150 nm of bilirubin in human serum. The combined role of energy transfer and noncovalent interaction highlights the potential of the new polymer design for highly selective sensing activity in complex biofluids.
Hydrogen-bonded drug conjugation is highly expected as
the next-generation
smart therapeutic agent that remains stable in biological medium.
A carrier design strategy of hydrogen-bonded drug conjugates as pendants
in conjugated polymer nanogel is developed. The H-bond acceptor uracil-functionalized
poly(p-phenylenevinylene) and 2, 6-diamino pyridine
(H-bond donor)-functionalized doxorubicin (Dox-Py) are
synthesized. Further, chemically cross-linked PPV-nanogel with hydrogen-bonded
drug complex (PPV-NG/Dox-Py) is fabricated. The presence
of triple-point hydrogen bonding in polymer complex as well as in
nanogel network is confirmed by 1H NMR and FT-IR. The hydrophobic
microenvironment offered by conjugated polymers backbone stabilizes
the hydrogen bonding in the nanogel network. PPV-nanogel/Dox-Py hydrogen-bonded conjugation facilitates higher drug-loading efficiency
(82%) and cancer-cell-killing efficiency than encapsulated drug, indicating
the superiority of the present design. Sustainable release of Dox-Py is achieved for several days in response to the redox
intracellular and acidic environment inside the cancer cells. The
proposed hydrogen bond conjugation strategy could provide a broad
platform for developing high-value nanotherapeutics.
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