NIR-triggered thermosensitive polymer brush coating modified intraocular lens for smart prevention of posterior capsular opacification

Abstract

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment.

Applications of surface‐grafted polymer brushes with various architectures

“…PNIPAM-co-PAA brushes grafted on intraocular lenses have been applied in combined photodynamic, photothermal, and drug therapy for the treatment of posterior capsule opacification, a complication after cataract surgery. 109 Such brushes were loaded with gelatin nanoparticles with encapsulated DOX and indocyanine green (ICG); after NIR irradiation, not only photodynamic and photothermal therapy effects were observed but also controlled DOX release due to the temperature increase and collapse of PNIPAM-co-PAA brushes (as shown in Figure 9).…”

Preparation of Environmentally Responsive PDA&DOX@LAC Live Drug Carrier for synergistic tumor therapy

“…After 24 h, the cells were washed several times with PBS, and then 10 µl of CCK-8 reagent was added to each well and further incubated for 3 h. The absorbance values (OD) of each well in the 96-well plate were measured using a microplate reader at an excitation wavelength of 450 nm. [31][32] Animal welfare…”

“…Male Balb/c mice were subcutaneously injected with 0.2 mL of 4T1 cells (5×10 7 ) in the groin area to establish the 4T1 subcutaneous tumor model. [31][32] When the tumor volume reached approximately 100 mm 3 , the 4T1 tumor-bearing mice were randomly divided into 6 groups (n = 6/group): PBS, PBS + NIR, DOX (4 mg/kg), PDA (4 mg/kg) + NIR, PDA&DOX (4 mg/kg) + NIR, and PDA&DOX@LAC + NIR groups. The aforementioned drugs were administered intravenously via the tail vein to the tumor-bearing mice.…”

Preparation of environmentally responsive PDA&DOX@LAC live drug carrier for synergistic tumor therapy

“…Untreated cells were used as a control group. After 24 h, the cells were washed several times with PBS, and then 10 µl of CCK-8 reagent was added to each well and further incubated for 3 h. The absorbance values (OD) of each well in the 96-well plate were measured using a microplate reader at an excitation wavelength of 450 nm 37 , 38 .…”