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selective drug delivery to cancer cells and increased accumulation and penetration at

                   tumor sites. The study also demonstrated that iRGD functionalization improved cellular
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                   uptake and cytotoxicity (Figure 5C). Meanwhile, Wei et al.   utilized microfluidics to
                   synthesize  a  novel  core–shell  hybrid  nanoparticle  with  an  siRNA  core,  which  was

                   shown  to  exhibit  strong  siRNA  protection  and  loading  capacity,  improved  in  vivo

                   stability  and  biosafety,  as  well  as  effective  antitumor  efficacy  (Figure  5D).

                   Balachandran     et   al.   106  developed   an integrated   microfluidic   chip to

                   synthesize aptamer-modified    biozeolitic   imidazolate   frameworks     (BioZIF-

                   8) for targeting  lymph  nodes  and  tumors  (Figure  5E).  Yan  et  al.   107  fabricated

                   a pH/redox-triggered mesoporous silica nanoparticle (MSN) nanoplatform for the co-

                   delivery of doxorubicin/paclitaxel (DOX/PTX) (Figure 5F). Microfluidics also shows

                   significant potential in tumor immunotherapy. Han et al.  108  used commercial devices

                   (Dolomite)  for  fluoroconjugation  of  EGCG-ligand-siTOX  nanoparticles  to  regulate

                   tumor cells and exhausted T cells synergistically. Moreover, 3D-printed microfluidic

                   devices show significant promise for advancing drug delivery across the blood-brain

                   barrier.  Therefore,  by  integrating  advanced  microfluidic  platforms  for  precision
                   nanoparticle synthesis with conventional antitumor drugs, the resulting hybrid drug

                   delivery systems can significantly enhance therapeutic efficacy and targeting specificity.

                   This  synergistic  approach  leverages  the  tunability  of  nanocarriers  and  the  proven

                   mechanisms  of  chemotherapeutic  agents,  offering  a  promising  strategy  to  improve

                   cancer treatment outcomes.

                       Similarly, the integration of 3D printing and microfluidic technologies has led to

                   the development of microfluidic 3D-printed scaffolds, a groundbreaking strategy for

                   addressing  post-operative  tumor  recurrence  and  facilitating  tissue  regeneration.  A

                   notable  example  is  the  work  by  Zhang  et  al.   109 ,  who  designed  a  light-responsive

                   platinum  (IV)  (Pt(IV))  prodrug-loaded  scaffold  using  a  microfluidic-assisted  3D

                   printing  approach.  The  scaffold,  composed  of  polymerized  gelatin  methacryloyl

                   (GelMA) (Pt-GelMA), exploits the photoconversion of low-toxicity Pt (IV) to highly

                   cytotoxic Pt (II) species upon irradiation, enabling localized and controlled drug release.


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