The most common and most likely answer to this crossword clue is the 9 letter word NAGGINGLY
N
A
G
G
I
N
G
L
Y
Buddy explains!
The straight part
We know that "with no let-up" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case with no let-up = naggingly.The cryptic/wordplay part
In cryptic crossword there's often an wordplay/cryptic part as well.This part involves a more complex hint, such as an anagram, homophone, hidden word, etc.
Sadly, We don't have an explanation for this specific crossword clue yet.