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ATP Driven Pumps I: An Overview01:27

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ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
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ATP Driven Pumps II: P-type Pumps01:34

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The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
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ATP Driven Pumps III: V-type Pumps01:30

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V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
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Secondary Active Transport01:55

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One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
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Primary Active Transport01:47

Primary Active Transport

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In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction...
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PEGylated Heterofunctional Dendrimers Enable Multivalent Diclofenac Delivery for ROS-Driven Anticancer Activity.

Arunika Singh1, Natalia Sanz Del Olmo1,2,3, Michael Malkoch1

  • 1Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm 100 44, Sweden.

ACS Applied Materials & Interfaces
|February 10, 2026
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Engineered dendrimers effectively deliver diclofenac, an anti-inflammatory drug, as a cancer therapy. The nanocarriers show improved cancer cell killing and reduced toxicity to healthy cells, offering a promising drug repurposing strategy.

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PEGylationROS activityanticancer therapeuticscovalent conjugationcytotoxicitydiclofenac repurposingheterofunctional polyester dendrimers

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Area of Science:

  • Nanomedicine
  • Drug Delivery
  • Cancer Therapeutics

Background:

  • Cancer drug development faces high costs and limited success, necessitating drug repurposing.
  • Diclofenac, an NSAID, shows anticancer potential but has poor solubility and rapid clearance.
  • Novel nanocarriers are needed to improve diclofenac's chemotherapeutic suitability.

Purpose of the Study:

  • To engineer PEGylated heterofunctional polyester dendrimers (HFDs) for controlled diclofenac delivery.
  • To evaluate the anticancer efficacy and selectivity of diclofenac-loaded HFDs.
  • To investigate the mechanism of action, including reactive oxygen species (ROS) generation.

Main Methods:

  • Diclofenac conjugation via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC).
  • Peripheral PEGylation through anhydride esterification.
  • Characterization of G1 and G2 dendrimer constructs (G1-(Dicl)3-(mPEG)6 and G2-(Dicl)9-(mPEG)12).
  • In vitro evaluation of cytotoxicity in cancer and fibroblast cell lines.
  • ROS level assessment and mechanistic studies.

Main Results:

  • Amphiphilic core-shell nanostructures with hydrodynamic diameters of 170-330 nm were formed.
  • G1-(Dicl)3-(mPEG)6 showed significant cancer cell viability reduction (50-70%) at 1-10 μM with high selectivity against fibroblasts (>20-fold improved therapeutic index).
  • Both dendrimers induced ROS at significantly lower concentrations than free diclofenac, correlating with cytotoxicity.
  • G2-(Dicl)9-(mPEG)12 demonstrated potent but cell-line-dependent activity.

Conclusions:

  • HFDs are a versatile nanomedicine platform for repurposing drugs like diclofenac.
  • The G1 dendrimer offers an optimal balance of efficacy, selectivity, and translational potential for cancer therapy.
  • ROS-mediated cytotoxicity is a key mechanism for diclofenac-loaded dendrimers.